BIOCHEMISTRY AND
`
`MOLECULAR BIOLOGY
`
`_:
`l
`
`General Editors
`
`A. D. Smith (Managing Editor) University College London
`5. P. Datta University College London
`G. Howard Smith University College London
`P. N. Campbell University College London
`R. Bentley University of Pittsburgh
`H. A. McKenzie University of New South Wales, Australian
`Defence Force Academy, and the Australian
`National University, Canberra
`
`Subject Editors
`
`D. A. Bender University College London
`A. J. Carozzi University of Queensland
`T. W. Goodwin FRS University of Liverpool
`J. H. Parish University of Leeds
`S. C. Stanford University College London
`
`Oxford University Press
`Oxford New York Tokyo
`1 997
`
`Page 1 of 5
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`Astraleneca Exhibit 2017
`
`Lannett v. Astraleneca
`
`IPR2015-01629
`
`Page 1 of 5
`
`AstraZeneca Exhibit 2017
`Lannett v. AstraZeneca
`IPR2015-01629
`
`

`
`0.\jf."Jrd L"Jr:'I'c'r.s‘f{v f’:'(=.\-.5. (irrz.-.' ("1'm'enr!un Sm'c:. ().\;fEJm’ OX2 ISDP
`
`O_\j[r:m' N:'u' ]’ru'R
`Atimm Am':'\‘:'mm’ Bcn1g.F(m'.' Begum Bomhar BrmIr:.vAf:'<'s
`('m‘:-mru (‘upr Tmrn D(rJ|':*.\'Sn1mrm Dcflrf Finn-n¢*c I-.’:mg Krm,::
`.".\':m1.F:u.f Km-m-in‘ Krmrr f.um_:mr Mmh-c:.u r'|4rra'I‘J'(." a'y{e!bnm'nc'
`Mv_\':'c'u (‘ir_..- Nu.-'r'r:.’:I." PrH'r'.\‘ Sr'ngu;‘:ury ’.""m'p(».«‘ Tnk_I-‘a Tmwmm
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`mud ms-ucia.rL'rf mm,rJmrI'(*.\' in
`Bcrfirz .".'mdrm
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`in he irf(*rrff,f'Fcn' as mm'mr.\‘ u_,f'!.’.=:'.v uwrlc.
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`AH rfghtx n-.\’crw:.‘. N1: pm‘! u_,('.fIH'.\' _nm'n"I'r(rrr‘rm may hc
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`_,f£n'r n'crr.'r'ngfm‘ (Irv pr.'J'pu.\w rg,"r'c.wurrfr or _:Jr'i1»(r.rc.s‘mdy. or :':':'H('f.m: or
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`h'rc::ce.s' i.\‘.s'rwc*r.I' by the C‘tspl-'r'f.::I!! Lfr-:'n.w'rrg Agw1:'_1=. Em_mI"rfcs ('tJl1('(‘J'irM_ff
`P.-:pi‘ruIun‘:'n.:r rmr.s'ia':- .f.'m.\‘a m1:Ir.v mm’ in other munn'ic'x .s'h(mF.n' be .\‘en.' in
`thy Rr'g.‘r.'.\' Dc_n:.-rlmmai. 0.\j/Md Um'I=(*:'.w'1_v P1‘;-ms‘. at the adrfms'.'.: m‘1mr(-,
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`by 11‘a_1'rqf'rr'mfcm-u.'."m‘u-Ltc. he Jcm. n’-.s'o!:.“. fzircd um. 01' rJHJ'<’I‘II'r'.i'L’
`u'r':'r.'fumr.' wr'rfrrm.' Hm prr!>I.-‘_s'.':<’:-‘s prim‘ c'mr.a'<.’nr in crH_;: farm r:_fIn'm!r'ug
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`A ('u.'uI0gu(’I‘:*(:(1r'(U?Ji‘ rfr:‘.s' bank is rn-crffr.-!2.’c_/i"mra the BJ'iri.\'h Lr‘brru{r
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`La‘hm:‘_5- nf C.‘0:1_1u'm'.x' Crmn'ag:'ng in Pru‘:I.-'mr:‘¢m Drm:
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`ISBN 0 M3 854768 4
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`§"j1-pawn’ by Mrxr-kc! Hrnaxc Brrrficx Ma’, 2f,1'fm'iJ:rr‘_1‘
`P:-inter! in Grrm B:'fmr':1 by
`Bum’: sf: T(H'1J'i£’J' Lm‘, I-‘rmm-
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`Page 2 of 5
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`Page 2 of 5
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`coupling factor
`
`I5 pmpuI‘tiuItttl In the 1l'|‘.l}_1t‘ttiltt.lf.‘ til‘ the spiu—spin coupling c0n—
`stunt.
`:.tl‘t]u‘ cit‘ the
`l
`coupling factor (t.lJ.lJ.r’..‘ CF: ¢ttw'it.'t't’ l'('l'l'H‘;li‘Jl' eitht:t'
`pmtcitts t'tint.-tinniitg in the cottplitlg ul‘ All’ H-}'1Ill1L‘.'~‘l$ In elec-
`tron tt'ttti:apn1‘1 in mi1oL't1nnt.lrl:t. (‘til
`(.‘l~‘4 tll'C ohsnletu iitiim.-5
`For the u ti subunits tit‘ i11ltuc|1mn.lI'iai| H‘-transporting ATP swi-
`those. 2 amy til' the |'.tI‘0lt.‘lIt.‘i
`I'Ct|1Ilt't‘-tl
`lint‘ the muplitig 0|' ATE’
`sytttltesis to the ]')l'It.‘ll{!lI‘tt.lt.lt.:t..'(.l clcctrun l|‘€ItI5pUIl
`tn chloro-
`plttsts t.lIl1'lttg pltntnttytttlicxis. Tltrc coiicepl has been t'cp!;icL'tl
`l1 y the chemiosmotic conpting Iiyrptllesis.
`in Wl1.lL‘l1
`i1im1il1t':iiit:
`coupling membrane tI1't)' hitilngictil
`t!l'|!.!l'g}"-_\r'lt.'lt.'.llI't_i:‘; nntl
`cI1crg_v—I‘cqLIiI‘iI1g hiticlttuniistil prnct:sso::
`uccllt‘ lt')gDlllL‘1'.
`covalenca m't:uVt1lI.‘rII::I’ imnioniu vattcticc bctweeti two lilltmrt in
`t-1Clltilttttlill¢0I11DtJltlttl. t.‘l1ill‘iIt:li.‘.t’t/.t‘.tl
`lay their slitiring ultmc or
`l1‘tt.‘t1‘t3 ClCL‘Ll‘Ul'I5. —c(tt‘tt|L-Ill mi_’i.
`covalent hand it L7l‘||t!lTllL‘:Il l:IIJml i‘m'metl between) two ulrints in it
`titolcctlle hy the .~:ltttt'in,i_; nt‘c|coIt'oris:_ ttsitetlly in pairs. by the
`bnndetl :llt)ITtS.
`ts:-Itatlysis til‘ any rcttctintt lI‘t whicli tht‘
`covalent catalysis ll1t.'
`sttbstrattt:
`is nmdilicd by i'uI‘11‘tiI15 t1 ctwttlcttt bond with the
`callttlysl ltznzytnc).
`til‘ column chro-
`covalent chromatography any tecliniqur:
`matography in which the stttistttttcc oi’ i1ll.Qt‘l!§-'1 binds ctw:1|t:otl_v
`it-ith grnl1p.~:. o.g. —Sll gJ‘t‘tt.l[tS.
`t1I'l the stippnri nictlium and is
`sttbseqtttrtttly Lll5|)lHCC(l by {Hi tipprtimitttc |'t3&1gt‘I1I.
`covalent lclosetll circle (of DNA] or comleiitly cluztcit circu-
`lar DNA m' closed tltitlblc-strtttitlctl DNA uh.t'ii'..‘ t:t:cDNA‘. titty
`dottblc-slrattidotl DNA nmlcctilc thtit is L'i1‘L'1.I|ti1‘[ht1t I‘t()1I'tt.‘CE.‘i-
`ttztrity gcutnel:‘it::Illy circ:u|'.tr} unit
`in which both ]"IOi}'l]'tIL‘~
`lentitle sl1:Iml.~t ttrc uontplclcly cntltilitltitls. {'ruti;:(m' Hershey
`circle. open circle.
`covalent modification tiny til‘ it. diverse i_1t'oup 01' pt'ot:esst:.~: in
`which the initially s_vnt|tu-sized structures at‘ hiUpuly'I1‘lL‘l‘.‘:. espe-
`cittlly CIW._VlTIL‘b. prueitzyliicit. or strticturttl niticroimilcculcs. :u'c
`C11Z}'II‘tllI'.tll}-‘ tnntlitiocl hy the brcttkaigc uI'r.'m'tI1ent h011t|.~t M [Ito
`tttltlitiml
`til‘
`ttcw covttlcntly linked grnttpx It
`i1'IL‘l1I(lCS post-
`trartslational modification. The term may mitmtiincs he used in
`the more t‘t.“-tlt‘lt!1.t.‘tl sense of rct-ci‘:tih|c lI1l(‘l't.‘(‘m\"CT‘.\'ltJll ul‘ 2It:—
`live iII'Itl inactive t'nrin:; ol‘ certain tncttihnlic: L!|'t7_\"l11d.‘it‘trtlll't|'£I‘
`proteins by sale oi‘ cnnlrnl citzyitics. often by pl1usp|tnt'yl:i~
`lion (.l.C|)ll(l5|')l'lt'II‘)"li'tlit)I1.
`covariance an
`t1'It}zt3iLlI‘t.‘ of the nssucititimi hetwccii
`twu \ttlI'l-
`I-llJlt.'.‘5. For It pairs nl‘ vztlucs at‘ two t’?liltlI_‘JI1‘| \-'-.trittli|u::t. x um! _i'.
`this is given by‘.
`1]
`_'t‘}ltti
`.\"I{_i’
`(‘mu t_\-.1-3 = t.\'
`,1'. rc-
`\' ttI‘tI.l
`:I1‘t1 the ntouns ot‘ the populttlionst nl'
`where ,i- and _i"
`spcclivety, (‘tmiprirr correlation coefliciant. regression coefficient.
`variance.
`cuvnrion till)’ ml‘ the codntirs in :1 given gene ihttt tutiy t.'m1c<m1i—
`tttntly wiry. so resulting in l‘it\«'olIi'ttb|c I't'Itll.:Ill(‘It'I.\ or in mutil-
`tions lCtI[lt]'Ig to tttt1ii1n.ttcid §ltl‘ISlill1tlt11‘JS that llEl'i’L’ little or no
`el'|'t:i.‘I. [From Cntiuntttittttttly vttrizthlt: cntlm1.]
`covirus any virus that Cxlats mt two in more scpttrtttc ptirtictes
`:t|lt':|‘wI1iclt must
`lJt.'|1t't.'.':t:FIl. Iugt.-titer in the host oi'g:utism I'm‘
`the uutnplete I't:|'.‘Illt.'tIIlt_1I1L'yt.’lt! nflhe virus to occur.
`covolume the tttuuunt by which the :!|]pEI1‘L‘l1l vulumc u|':i mol-
`ecule t‘.‘i\:t3t3tl§ the i-tutnnt't|1c vnltttnes oi‘ the uzun.-ttituent :tl.L‘I]'It5.
`It is Llslltllly I3 I-‘l cm‘ rnol
`'i'm‘ pt'uIeiIt l1‘lt1lL'L‘ltlI.!S.
`til" {I
`cozy:-nase originzi||y_ tl1:,-
`l1t:alI-$litl')lt.:. dilTttsih|c l't'att:timt
`L’!'1ILlc ztqnoous L‘)tlI'LtL'l oi” l7I‘t:wt:1‘s’ yet-‘tst
`thtit.
`ii‘ ztddcd In the
`ltcztt-ltthilo. 1tondiI'|'u.~tib|c |‘t'tn:tiott tzytiittsct. Wutthl clttthlo the
`zilcnltolic lc:‘I1tctittttt0n of glticnst:
`tn occur In at cell-I‘t‘cc 53'5-
`
`ti:m_ The term was sttlisetitieittly tipplletl In out‘ put uultir subv
`stttttuc p|'c5cnl
`in that
`I‘i';ti:liun. new ltiiown as nicotinarnitla
`adenine dinuclautide.
`C3 pathway .tHl' rlIl.ft'l‘llrI.llt't‘ tttHilt' jttr reductive pentose phosphate
`cycle.
`C4 pathway .-m m’.'t-r.Ittrrft‘r itrnm‘ ,I"ut' HBtt‘.'lt—Slat:lt pathway.
`CPBA uttifar. _,t'm- i:ompt:Iiti\«'c prulcin-Iaintllttg :i:t:iti_v.
`
`C-reactive protein
`
`CPE tfnlJlllt". _,fiu- cytnpnttiic eI'l‘cv.-t.
`t‘i'nni ptoinsnlin
`C peptide 1
`it the l[ltItIll\'t: polypcptitlc uetciscci
`during its l.‘(.|ll\-‘t.‘1'Si()11
`to insulin.
`It cimttiins Tit Elll‘tlllt1-:lL‘iLl
`resitltics in the ltuinun but shows grenter ~'p-zuies. vtiriuhility in
`lmth length -'tI‘tt.l
`;tI11iIln—'oL'itl
`.‘iL‘L'll.|t.‘t'lt.'t‘ thtin t.lL)L'$ 111sLIli1L Tim
`sIt'ui:lurt: til‘ ptiruzint: ('—|it:|1tiLle is tittclutling the Iltinkiiig laatsit‘
`I'C$lLlllct-ill
`R it |.fAON|’QJ\(iA\"|£LGCi(il.fi(t|_QA LA |.lCGI‘|’Ql( R.
`It is l'ClCit$t‘(l into the h|nm|.~;trc:tn1 t:unci.iniit:I11tl_v with insulin.
`llt.‘I‘iL‘t: the l1l<1t'ttl level is LI.*tcl"tt| in L‘V:IltI.’Illt.‘It1LIl'li—|JUll l‘tinctiun_
`la thttl Hcgltit-ttit ml‘ the }1I1]ll‘|tl-‘tt.(.’lLl
`.~‘t:t|tIt:I1t.'i.‘ ni‘ pi‘uiI1:tlL|iII lying
`,_.
`
`hL‘lWet.'I1 the two l'CHlllL|L‘l\‘
`tlL‘SllI‘ICLl to l‘.tl.'t.‘(ltl]t.’
`t'L‘.\|‘tL‘t'l.l\r't;’ly
`C-lL'Tt'lillttll resttltlu ml" the B L'l1:IlIt Dllll1.*i1Illl'I anti
`the N—Icrn‘Ii-
`nttl l'L‘§lLll.IC'Ul'll1I.‘ A L'ht'tin.
`it consists .~ttt'tIct1II'tIlly tiI"l|1:: tll'J(t‘."t2
`|]t)i)‘pL‘]‘JllLlC :‘i|LI.\‘ twn l'ltmkint_1 pttits 0|" htisit‘ I‘L‘1\‘lLll.lt.‘S. [‘ pop-
`llLlt: 1:: n.‘ItnL'd i‘I'ut'n L‘(‘|I1[lL‘t'.‘1ll'|l_1 pcptitlc. and pt:t‘|1up:t also be-
`utttsc.
`‘.tl‘1t:r A {chain} ttnd I3 [chain]. C l[‘Jt?}‘Jll(lC]
`I'(§|1I‘C3s‘l!IllS
`.'1|p|1:t|Jc1ic:1lly the llllrti mtijnr slt'tti.‘lut'et| utitiipnlictil nil‘ pro-
`insulin_ 2 mi n'.hIlil('l'lln‘ln'tll't‘ rmmv ,I"r;i' C ltzigtnuttt
`tt:t‘ji—|i|mtt'nptit]
`t.w:- lipotruninj.
`lt high tlcnsity 0|‘
`3 lth t.'('IIIl:lll1lI‘ll:
`l
`CPG island :1 region ral'
`Inctltylittctl cytosine rcsitlttes and LIL‘l.'l.ll‘I'lI1g_illlltlctlllttclitt 5'
`l:.:
`C]
`rcsitlttcs. LC.
`in the st:L]ttL‘n¢:i.:
`I‘C'p(}_ ('pG lstttntis are Fre-
`t.|LICIllly Found in :I11in1:Il gcnniitcs at
`the 5' end :3!‘ genes.
`In
`nltinta thr l'I'lCll'|}'lillt:(i scqllcttuu is ...E‘pNp('}p... wlicn: N Ctlll
`be any lnttse. Mclliylztlimi 01‘[)NA it 1!
`lit'i'tttiblc plictttitttizttutt
`that |'Ctl1IL‘ES gum‘ u"<p1‘L:ssi0:1. pI'nh:Ibi3' lw im:i‘t:ttsing the hinti-
`ing at" it i'cpressm‘. (‘[16 iSl:ltltl.‘i are it site uf' high In Littiticutzll
`I‘:-rqticncy ht-utiustc eipontoncotis tlctttnintitiun til‘
`the methyl-
`itled cytosine gives tliyntino. which is not t‘t‘t.’t.)gl1i!.(!tl by DNA
`i'ep:i'ti'et1'z.ytm~s.
`C3 plant tiny plant in Wl‘tit.‘l] fixtttinit nt't::i:'butt diuxiclu ticuut-5
`|.3I'|.'Ll01l1.ll'tEltlIl}" by the reductive peutose phosphate cycle: i.u_ by
`ll1t:tJr[It.)l‘:I1lm.'i
`initially into the t|irr:::—-.-zirh-an CUlil|‘l0l.ll1Ll 3-
`pliusplltigly-2:.‘rttlc.
`C,‘ plant any plont in which llixzttiun ul' t::lrhnI'I dioxide I.)C.'i’.'lII'i
`pmtlcltnlmtitlly by the Hatch-Slack pathway: Lu
`h_v lt‘It‘nI‘p0l'tt-
`tinu inititilly into the l'utti‘—uttrhmi cuinimuncl
`tixttluttcetttte.
`Sucli pl:-tnttt IIFC lnttntl ustizitty in soittittrid ctmttitions with high
`light levels. They in:-ttitle sugar utine. corn ln‘I'ttl?t:J.
`.’tl‘tt‘l miiny
`weeds.
`cpm n.-‘t:.]1.In. trt'rl1t'. _)'i:i' l.‘t!l11115 per mitutlc.
`Cr .-.g1'ui.'m! fur ultmniiotit.
`Crabtree effect the inhibition pl" :'cspirzttion by gtycolysis.
`llhc inhibition is small and t'1CL'lIl‘3-i only in at
`low types. of cells:
`that
`|JDS§E:5i.‘s 3 high glycoly it L‘up;tL'ily. cug.
`tl!~'t.‘llCS tutnnur
`cells and other ncopltisttt:
`tissues. renal
`tiicdulht. lcttkoeytes.
`ElI1Ll c'.irtil;igt:. ('n.Iiipiit':' Pasteur effect.
`Craig apparatus the n1n.~t1 widely used type of il‘p}‘Jit1'tllLl5 For
`
`ca
`ing nut countertturrent distribution Cx|3t!I'll‘ti{.‘lilS. The t.'ttTlit:I‘
`verstmt (I9-‘l-1) want t.IOIiSll'llt.‘lCLl oi‘ 1‘I‘tCl.1tl illltl the ltIlt!1' V€1‘.‘ilt‘Jll
`EH34‘); win: of nmclulttr clceigtt and CDI1.SII‘t.IL‘lt.‘ti nl' glass. |AI'tot-
`l-ym:ln (‘rt-tightuti Craig tt9llta '.l>'ll.]
`crambin ti protein obtttincd t'r0iTt Hcetts til‘ (‘mni."w uh_i-.\-.w‘iii‘t'it_
`IL L'GI‘t'l|'3I‘l5t.!S Jti t1t.t1ll1t.! acids. ltilii .'t mn|i:i:LIl:I1‘I11:t.-H: 01’-1-.7.‘ kl)tt
`tdztttlltttse uncle (‘Rf-\M_C'R.t\AB).
`ttntl
`is FCIl1£lI'i(.'rllJlt.‘ for its
`highly ¢)I‘t.lct'et|
`t.'t‘)'.‘il‘.ll.‘a' aintl very l1igl1t‘e::nlLItiutI. Its 3-D struc-
`ture is known.
`cranin it Fm-in oi’ dystroglynan.
`CHE rthhr _fm' cyclic: AMP I‘t:S|30fl§ic clement: ti nt:qtIt:I'tcc
`GTE}AL'('}’|‘|/\i'G]1AfGI.
`It
`thttt is presctit in li'l'rll‘ly viral {.lI'tl.l cttllultir |1I‘Dt'I10li.‘l'5. Vt-"tit-ii
`lnimis CREE protein. lI‘:tn3tcri|'tlinI‘t :1l‘Iht‘ genes I'L’}_1ltlitlI:Cl
`I1-.
`'-.Iu ti
`:1 |1l'tJt'|'lulCI‘ is turned mt,
`C-reactive protein :.'Mrr.' FRI’: on llL‘lt.lltI, L‘I‘}"-‘§llllllZEIl}lL tic.-it
`sctisitivc |'!l‘0ltJl|1 til‘ =| I8 kD:t that is (lClL‘L‘ltIl‘tlt.‘
`in liutnttlt or
`nmnkcy hlontl .‘il'.‘|'lll1'I early in the i:uur.~:e at‘ various’ itiftltztiotist
`
`or when there is itithttnintttioti.
`l.l!t.*ilti!
`tlttnnlge. or lll.3(.‘.l't1.t-‘t
`.
`(‘Inn at‘ the 50-t.".Illt!{l acute phase proteins.
`it
`is nnrmitlly un-
`
`Page 3 of5
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`Page 3 of 5
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`
`Lig
`
`Lig.S'_lr'Ill/)()/_/'01‘ the lignoceroyl group, (.'il3—[Cl'l;'l;3r CO
`ligancy (I
`lost‘ (‘UIJIIIIUII (I/tt*i'ri(i/r'iic rru/rit*_/‘or coordination number
`(def. l).
`|igand l (in t-/iwrit'sIt[i') (in a simple inorganic compound) any
`individtial atom. group. or itiolectile that
`is attaclied cova-
`lently to the cliaractcristic or central atom or moiety. 2 (in an
`organic compound) any individtial atom or chemical group
`that is attached covalently to a specified carbon atom; are (!f.Yi)
`pointligantl. 3 {in ltimi/it'rrri.rIr1i') (in a coordination entity) it any
`individtial atom. ion. or inolcctile that is attached coordinately
`to one central metal atom (tinitlcnt-ate ligand). b an ion, inol~
`ecule. or moleculargrouping that has more ihaii one coordin-at~
`iirg grotip (bi—.
`lri—. or tnultitleiitnte ligand).
`In both cases the
`ligand is an electron donor lit the formation of one or more co-
`ordinate bonds. 4 an ion of either sign that can associate rc-
`versibly with one or more (charged or uncharged) atoms or
`elitiractei'istic molecular groupings in another (usually larger)
`molecule (as in the hydroiiatioir of a conjugate base, the coor-
`dination of a metal cation by a protein, etc.). 5 a molectile (or
`a class of molecules) that has become linked covalently to an-
`other molecule to form a conjugate, whether in a single—step
`reaction or by stepwise addition of its components (e.g. an
`oligosaccharide moiety in a glycoprotcin). 6 a molecule (or
`part of one) that is bound or is able to bind selectively and
`stoichionietrically, whether covalently or not, to one or more
`specific sites oti another inolccttle (as in the combination of
`antigen with antibody, of hormone with receptor, of substrate
`with CIT/.yl1tC.ClC.).
`Iiganded bound by or as a ligand or ligands; ligated, we ligate
`(def. 2).
`ligand exchange (chromatography) a column—chromato—
`graphic technique 111 which a cation-exchange resin is loaded
`with L‘ complcxablc metal ion and the resulting loaded resin.
`which retains the capability of the metal ion to coordinate to
`an appi'opriate complexing agent or ligand,
`is used for the
`sorption of that ligand from a solution or a gas phase. lilution
`is then effected by displacement with.
`i.e. exchange for. an~
`other ligand. The resin is commonly a chclating resin (c.g.
`it
`styrenes divinylbcn1.ene copolymer
`to wltieh iminodiacctate
`groups are attached) and the ion is usually of a transition
`metal (e.g. copper or nickel), such ions tending to be bound
`strongly to these resins. Separation ofcomponents of mixtures
`occurs by virtue of the differences in the stabilitics of the vari-
`otis inetal»-vligttitd cotttplexcs formed.
`ligand-field theory (in irro/gtgurric ti/rerirr'.i'ir'_igl a theory, closely
`related to the valence-bond theory, that deals with the c ccts
`of ligands on the energy levels of the central atom or ion in
`complexes and crystals. it is especially useful in interpretation
`of the spectra of inorganic complexes.
`in a cell membrane
`ligand~gated describing an ion cltitnnel
`that is caused to open by the action of an agonist binding to
`the receptor that governs the clranitcl. Channel opening ‘an be
`direct. when the receptor acts as an ionophore, or indirect, in~
`volving a second messenger regulated by a G—protein.
`Iigandin (I imrrtc,/i1i'rr1cr'/ygiven In a basic dimcric protein of'~'2
`is
`kI)a per diincric subunit
`(see gltithathione translerase).
`It
`abundant in rat and liurnan liver, kidney. and small intestine.
`it binds with high altinity to heme. bilirtibin. and other or-
`ganic anions. polycyclic aromatic carcinogens. and various
`metabolites.
`in addition it catalyses the conjugation of glu-~
`tatltione with a variety of electropliilic substrates, shows sele-
`niiiin—independent glLitathionc-peroxidasc activity and steroid
`isom'
`' sc activity. and covalently binds activated metabolites
`of several carcinogens. Ligandin corresponds to the 0 class of
`glutathionc traiisferase. Ligandin is present in the pars rccta
`of the proxinial renal tubules but does not norinally pass into
`the urine: its presence in the urine. ligandiniiria. has been used
`to follow the evolution of various forms of kidney in_jtiry,
`while its presence in serum provides a sensitive indicator in
`liver injury Also variously called Y protein, organic anion
`binding protein, basic
`117.0-ti)/C binding protein. cortisol
`
`light chain
`
`metabolite binding protein (binder protein l). gltttathioiic—
`transferase ll.
`liganding binding by or as a ligand or ligands; ligating; sue lig-
`atetdef. 2).
`Iigandinuria .\'L"<’ ligantlin.
`i-m-r'mrr of affinity chro-
`ligand—mediated chromatography tl
`matography that cmploys an additional component. the affinity
`ligand. which is a ligand both for the reactive coiitpottcnt at-
`tached to the insoluble inatrix and for the substance to be pu-
`rified. Because the ligand may readily be
`renewed after
`completion of each separation. the method is particiilarly use-
`ful when the substance tiscd as the ligand easily becomes de-
`graded or iitactivated during the course of a ptirificaiion.
`ligand—receptor assay a form of saturation analysis for a hor-
`mone or other agonist wherein the specific binding agent used
`is an isolated preparation of the naturally occurring cellular
`receptorsubstance for the agonist. An advantage of the assay
`is that the values obtained are considered to be a direct reflec-
`tion of the biological properties of the substance assayed.
`ligase 1 or r’,/‘oi’/t'rt'r'l_iv') syittlietase //'l(’ .sji’.\'IL»'rIirrIir I‘/(I.\‘.i' r'i(rrir('_[or'
`enzymes of class EC 6. all of which catalyse the ligation of
`inolcctiles of two substances with concomitant breaking of a
`dipliosphate linkage in a nucleoside tripltospltatc. The recom-
`mended names of particular ligascs are formed in sortie iii-
`stances. especially those of enzymes of subclass BC 0.4, by
`using the generic name earboxylase, e.g. pyrtivate carboxylase,
`11C 6.4.1 . l. In the remaining instances the generic names ligase
`(def. 2) or synthase are used. according to whether the name of
`art individual enzyme is to be based on the names of the reac-
`tants or on the name of the product, i‘espccti.vcly. 2 (l gciierir
`rtairie/'01‘ many cn7.,yntcs of class EC 6 (see ligasetdel‘. 1)); when
`added to the names of the two reactants whose ligation is
`catalysed by a particular en’/.yine it forms the recommended
`name of that en’/.,yme; c.g. tyrosine —tRNA ligase (EC (i,l.l.l ).
`acetate —CoA ligase (EC 6.2.l.l). Sac (I/.i'U synthetase (def. 2).
`3 .\'t'(‘ DNA ligase.
`ligate I to join together. especially with a ligature. 2 (In r‘/re/ir—
`t'sIrjii)
`to join (molecules or inoleculttr fraginents) together
`with a bond: to coordinate. 3 to bind as or to a ligand or lig-
`ands. 4 (iii .i'tri'gi'r‘y) to tie off (a blood vessel or dtict) with a
`ligature so as to occlude. ——ligal‘i0n rr.; ligatable ml/‘.; ligative
`ml/.
`Iigatin a filameirtous plasma rncntbranc protein for the attach-
`ment of pci'iphei'al glycoproteins to the external cell surface. it
`acts as a trafficking receptor for phosphoglycoproteins. local—
`izing them. after iirtei‘nali2.ation, within cndosomes. Example
`(fragment) from htiman: database code LlGA_HU.\/IAN. 75
`amino acids (8.47 kDa).
`light I electromagnetic radiation capable of producing a visttal
`sensation in the eye.
`It comprises wavelengths in the range
`580 78!) nm (frequencies 385 789 'fll'/.). although the term is
`soitictiines loosely extended to include some tiltiaviolet and in-
`frared radiaiion in adjacent parts of the spectrum. 2 tin t’/l(?Ill-
`r'.\'Ir_t'} describing any (especially nrctallic) elemeirt whose
`density is
`relatively small
`[usually <50tlt) kg in ~‘).
`3
`(in
`p/rt~.m'.r) of less than the usual mass. (‘rmnmrc heavy.
`light band a
`region of a muscle sarcomere that stains less
`densely in light microscopy and low—magnification electron
`microscopy relative to the dark bands; together‘, these differeii—
`iially staining bands give the striated appearance of skeletal
`muscle. The light bands are relatively isotropic in p0lari‘1.ed
`light; they represcrii the regions occupied by thin filaments. See
`(I/St! thick filament, 2 line.
`light chain 1 or 1. chain or (‘/iJl‘l7lt’l'f_l'j B chain S‘)?/It/7r)/I 1.; the
`shorter of tire two main types of polypeptide chain of an im-
`munoglobulin of any class. Ol‘ :22 kDa (human). each light
`chain is linked at its C‘—tcrininal cysteine residue by a disulfide
`bond to the constant region of a heavy chain. In any given ani-
`iiial species,
`light eltains may be distingtiislied serologically
`irtto two types. K and X. which occur‘ in iinmtinoglobulin iiiol—
`ecules of every class in proportions that vary only with the
`
`Page 4 of 5
`
`

`
`49!]
`
`peplos
`
`the peplos (Le. envelope [I.lci'. 3)) of nit
`of which p1'ojcL'I front
`enveloped virtttt particle. Pt:p|oiiiei's may have cell-rcceptoi-.
`henitiggltitiiizititig, or Itcttiiiinidiittise zictivily.
`peplos mt rii'.*:'i'ririt."i'u iir1iiw_{'111- eniielnpet1.tcI'_ 3).
`pepsin I
`tiny til‘ ll small Iinniily o|‘clo.»:cly i‘t:|t1lcd :I5p;1I'tic pro-
`teiiitise enzyines til" .7-l—3t'1 kD;i that
`togetliur give rise to the
`priiictpail protcitiiisc activity ol‘ gastric juice oi" vet‘tt:h1‘utc:s.
`The family includes pepsin A. pepsin B. pepsiii C ti.e. gestriesint.
`untl pepsin D. Pepsins have |‘l'I£I)tiI‘I1:ll nctivity ill pll viiltics in the
`ratngc 2 3:
`they prclr.-1-cnliiilly c:ila|y.se iiytli'o|ysis of |.iepti(!e
`bonds i'iJt‘ti1cd l'1‘nn‘t Iiydrophnhic ziniiito-tti:iLl rcsidiies. the de-
`tttiled specificity v’
`'
`ing lit1I'I1(.‘Wll'r1i hutwccii
`the diITet'enl
`pcpsins. 2 an m'tt'1'ii1in‘1-u i11i1i1..-_,'i21- pepsin A.
`pepsin A ut‘ pcpsiii titular-. rm r1’1'11.-‘g at r‘.’tr*ilti'.i'ti'_t'.i: PPS: iliu rut’-
`iiiiiiiiciirh-ni l'l‘tl'!H(’ fin‘ the predoniiiiaiit ciizyiiie (I3(.' 3.4.23.1 I ol‘
`the pepsinfzittiily. It
`is ‘rt :iiiigIe—c|1tiin pliosphnprotcin oi'tin the
`pig) 32? a1nino—a1cit| residues. |'oi'incd by liniitetl protcnlysis of
`pepsiitngcii A.
`It pI‘i:l‘ci'i:Iiti:t||y cleaves pcplidc l)t}liLi.‘1'- w|ic1'c
`the reititlties on either side are J"omied I‘t':JIi1
`llytlmphobic
`itmino ticids; For eittitiiple.
`iii the B i.:|i:tin oi" insulin it uicatvc.-5
`Phc'—|—V:1l3. Gin"-|-His‘. Cilti”-|-A121". Alli“-|-Lcii”. Lett'-‘--
`Tyi"".
`'l‘yr"‘-|-Lott”. City"-I-I’hc“"‘. P|ii:”—|—P|ic35. and I’|ie1-‘-|-
`Tyri" bonds {i'mitp:.'i'c= pepsin B]. The I.II‘t|')l'It‘:lli[‘)l'IUI’)tliilI3Cl Form
`o!”r1o1*1:i1ie pepitiii A is called pepsin D.
`pepsin B ur parapepsln I n pig l!Ili’.)'l'I'tE (EC 3.4.23.2} oi" the
`pepsin Ftiiiiily.
`II
`is
`n
`single-cliziin [_1l't0S]')l‘I0|‘Il'tJlcil'I oi‘ 332
`ztmiiio-acid 1-esidues.
`fnriiicd by limited pmtenlysis o|' pig
`pepsiitngen B. it hits little itctivily towards l'Il'.‘|Tl{')glt)l‘)iI'l‘
`'
`'
`strate (c'oiii;:rrr¢' gaslriesint. btil tlCg.I‘ittiES gelzitin. its spec!
`on the B cliain oi‘ insulin is more restricted th:1n pepsin A:
`does not eleaive P|1L"—f—\«";i|3. Glll4-I-l’ll5'r'. or City“-|-Plie”.
`pepsin C on rrfieriitirive mmtt'frii' gastriesin.
`pepsin D uitphosphoryliited pig pepsin A.
`pepsinagen zi p1‘ccu1'sor (i.e_ zyinogenj of 21 pepsin citzytnc:
`pcpsinogens A. 8. anti C give rise to pepsin A. pepsin B. ztncl
`pepsin C (Le. gastricsin] ttsrtcctively. Pcpsiiiogens are secreted
`lay the chief cells oi‘
`the gastric mucoszi ol‘
`\I'tlI’|ClJI‘i||t.‘S.
`In
`pepsiiicigcii. the active site is eotil'or1ii:1t1onnlly ni-.1sl<cd at neut-
`rul pH. and cxpmicd as the pi] falls after secretion into the
`siomiich. The I‘ir.~1t bond l'3I'i'.‘dl(iigI'..‘
`‘noses
`the 1'cle:1sc
`of‘
`residues
`I
`to.
`leaving a peptide known as pseiidopepsirt.
`Tliei'cn|'ter. B l‘tIi'tiiei‘28 i'e:.'idues arei'cti10ved in stages to form
`the iictive cn?.yn1e. ]‘1:psi1mgcii C is also SClIl'Clf.'Ll by the lTlI.I-
`eosa of the proxinittl dttotleiitim.
`lixtitnple from htimttni Untit-
`base code PEPAJILJM/‘IN. J83:iini1in:1cit|st4l.9fi kD:t): this
`is the pcpsinogcn prccLir.:or with :1 sigiial peptide; pepsin is
`from resitltic 63 to the end.
`pepstatin A N-i.-nwnleryl-L-v:1lyt—1—valy|—3-liytli-oxy-6—1ncthyl-
`4—aininoheptnnoyl—i.—:tI:inyl-J-liydroxy-h-int:tliyl-4-t1niiiio|tcp—
`tunriie acid;
`:1 peptide.
`isohitctl
`front hroth C|.ll[IJt'C!'i
`ut‘
`Sm-,11i11i11_1u-v.\‘ spp_. lhttl inhibits pepsin tind other uspai'tic pro-
`teinitses. notably czttltepsin D. reniit. tIl'Il.l Fungail tlL'lLi protein-
`axes.
`
`it
`
`peptaibophol 111' peptiiilitil any ol'u group of peptide iiinidc un-
`tibiotics.
`IS--24 i'csidue:;
`long and coiituiiiiiig tip to 4tl‘V.1:z-
`aniinoisobutyric aicitl
`iesidties. The I1'II.‘I‘l1l.)t.)I'5 ot‘ this group.
`cmcriinicin. zei'vtiii1ictn IIA. 1lI‘IllEII‘l‘llJt3l)ll'I
`I. sizuknciltin A.
`and alametiiicin. are all capable of uttering the |Jt£1‘II‘lE.'5lIIl.llly nt‘
`pliospliolipid hiltiyers. The N tci'I‘i1ini
`tire ‘r1¢}'l‘c'Ill.)Li atnd the C‘-
`terminal ctirboxyi groups are in aiinde linkage with pi1i.‘11y|-
`at-nninol.
`
`peptic 1 ol‘. pertaiiiiiiig to. csitisctl by. or containing pepsin.
`21-If pertttiitiittglo. m'pi'0n1oliiig tli_I__l.‘l£S|iOll.
`P'3¥“i"33BUJ'|lt'|tli(I1‘.'
`l|}'ilt‘t2IlEI5l'.'U."|Jr0ll'.‘1l!a‘i.' itny t!I'I1«‘!yl‘I]i! that |1y-
`tl 1-olyses peptide bonds. The group iIlt.'lI.ltlL‘E'i the exopeptidasns.
`wrli as the uiiiinopcptidnses mid L‘:Irht‘tl\'y|‘lC|3lld€tSt'.‘5.
`i$IJlJ-SlllJ-
`\ll:IR.‘tL".: EC‘ 3.4.lI
`It!) tIt'Itl
`the entlepepiiitlases (Sill)-§ul1t,'litSliL'5
`l:t_'
`."i.4.2I-LN}. The I992 I'li'Vl!\lUI'| of‘ E.-1:,i'ii11' Nrmir'iir'frt!i.-i'1-
`tpulilislied For IUBMIJ by Aczttlcitiic Pt‘e::ii]
`ithottld be enti-
`sttlted for moi'c detail.
`peptidese P-sites sitcs adjacetit to 111' near the L‘-lL'IIVL'tl site in
`
`peptidergig;
`
`in t|csc1'ihiiig the spcc'1I'icity oi‘ pcpti.-.1.
`pupliilalsc stilislriilcs:
`uses.
`it
`is useful
`to have a convention for ideiitilyiiig ti“:
`residties on eitltur slide of the cletived bond:
`the Following
`motli-:l
`is often lnlititved (the tflcovcd. or seisiiiie bond is iiidi.
`ciiled its -I-. ztntl the N tei‘mi1iti.~i is its ttsutil to the left]:
`-P3—l’2—I’| —|—l‘ I '-P2‘-P3‘-.
`('nii1,inii‘¢- peptiilyl site.
`peptide any etinipound ersiilitiiiiiig two or more tiiiiitio-acid
`residues joined hy :imide bondtst t.m- peptide bond) forinecl
`l'1-oin the i:21i‘hoiiy| group ol‘ one amino acid (residue) ttnd the
`amino group oi‘ the next one. The term peptide usually ttpplieii
`In coinpotiiids in which the amide boiitits} are Fortiied between
`(‘-1 of (tits: tr-ttiiilno acid tI‘t.:sidtte] il'tl(l N-2 of aiiiotlier. but
`it
`iiiciutleti cutiipounds in which the residues are linked by other
`aniide bonds. .S‘ci- «fin» oligepeptide. polypeptide. —-pcplitlie mifii.
`peptide antibiotic any mcinbcr oi‘ 21 divei'sc group of" iIt‘lll-
`I:-iotics coiiteiiitiiig ainino-acid residues. some of which are
`often oi’ the i)—I'o1-ni, linked to one anotlicr by peptide boiids,
`to liyclroxy acids by depsipcptidc bonds. and Frequeiitly also
`to ttdditiomil components: the structure is often cyclic. The
`group illcltltles the bacitteeins. graniieidins. pelylnyiiins. and tyre-
`eiiiiiis.
`peptide bond Ht‘ peptide linitiige tiny ninide bond t”or1ncI:l be-
`tween two ttlttino ncitls tor tllrllflfl-Elcitl
`residues}. The term
`nsiizilly denotes the ill.'l'IltlC bond (sometimes catlled the eupe[.i-
`tide htiiiil) l0I'Il1CCi between an (1-amino group of one uinino
`acid and un ix-czirboxyl group of nitntlter amino ncid. but it
`also incltideii any amide bond tsoinetiities called tin isopeptiile
`liundt Formed t'i'o111 an amino group and a carboityl group ei-
`ther or both of which are in other positions in the eontribttling
`amino acids.
`peptide chain r11-polypeptide chain any discrete linear sequence
`ol‘ arniiio-acid residtics linked by eupeptidc hniids, especially
`in :1 larger n'I0lCCl.Ilitl'§l1‘l.tClLII't:. .S‘ui- peptide Iiontl.
`peptide HI zihtitz: PHI; it 27-residue peptide ainidc. also to-iown
`its PHI-2'1‘. Found in intestinal tissue, |:1i'uin. respiratory tract.
`and puncretts.
`it stimtilates instilin sccI‘elioI'1 itittl pniici'eatic
`cntocrinc secretion. caiusezi vnsorlilation.
`increases inlesliiiitl
`fluid transport. relaiies smooth muscle. and is a potent pro-
`liietin-relenntng liictn-1'. It shows seq uonce lioniology with gust-
`ric inhibitory polypeptide. glticttgon. secretitt. and vttsoitctive
`intcstiniil |J0l_‘i'|'JI.'pl.l|.'ltiLiItIl11tIl'l PHI has the scqiir.-nsse
`I-IADGVFTSDFSKLLCSQLSAKKYLESLM-Ni-I3
`tpo1'L:ine Fl-ll l‘t‘.rlSi Ai'g” and lie”; bovine has 'l'yt'“’. Arg”. i|llL'l
`Ila”). It is named :1t'ter the Slliglt‘-lt‘l.lEI‘ codes. It and I. for the
`histidinc and isolcuctne residues at the N and C tc1‘1'I‘tlI1i rc-
`spcctively oltlie pDt'L'il1t.‘ll.|tt:l bovine peptides.
`peptide Iiistidine valirie 42 «him: Pt-IV 42: fl peptide with N-
`term'1n:1l histirline and C‘-tcriniiuil v:-tline. having 42 residties
`derived from residties SI-I22 ot‘ pi-epro-vasoaictivc intestiiiat
`peptide.
`peptide hormone or polypeptide hormone any peptide with
`horinonzil activity in ainiiniils. whether endocrine. neuro-
`i.'l11‘.lUCI'll]C'. or pl.tI’El.Crll‘|E. Such substttiiees Form 11 very diverse
`group physiologictilly. and the boiiiidatry betivccii peptide hor-
`mones and protein horinones is somewliut indistinct.
`peptide Iwdrolaseuimifn-1- iutiii<'_f'nr peptidase.
`peptide linkage I rm alt:-i't111i1‘ru iii.-iiii-_,tii1~ peptide bond. 2 chem-
`lctll linkage between s11'I.it:ti.titiI cornponents ol‘ it molccittc by
`ineaiis oi‘ peptide l30ll{lS.
`peptide mp at pattern. cliariicteristic or‘ 11 piirticuIiii' polypep-
`tide or protein. produced by p:irti:1l hydrolysis Followed hy
`two-diiiiciisional
`l"ractio11:ition oi‘ the i'csu|t:1iit peptides (and
`amino iiciilsl by chruniaitogrztpliy t-titdlor eti:1:t1'opho1-csis.
`peptide nucleic acid 11 synthetic DNA analogue with nu N42-
`antinoctliyltglyclne lJ‘rlt:l-ibt]l‘.tC that niiitiies DNA in Ioriiiing :1
`lielarciduplex.
`paplidergic I LIL-scribing any nerve thilt is nclivittctl by ‘.1 pop-
`tide agonisl, 2 de.~:L‘ri|‘JiIIg_ tiny nerve Ihttt acts by releasing it
`
`Page 5 of 5