Chapter 2

PE,PTIDE,S

40

Peptides

ln the reaction of carboxyl group (-COOH) of one amino acid withamlne group (-tIH2) of second amino acid the molecule of water is eliminatedand dipeptide is formed.

I

^lH+ [,,

--OHaN-?-"io-F{

R2+., rr l" JroHeN-?-(o-

H

pepti de hond

Cdipeptyde

l']

Amino acid (1)

Peptide bond

@t{

WaterDipeptide

Structure of peptide bond -

two isomeric forms

H

H

H

H

42

H\dj0/Y

,'o:c\*. -=-')#ry-

H

The peptides are the linear chains formed with amino acid residues subsequentlyconnected with peptide bonds.Amino acids residue (-NHRCOOH)

- chemical specie derived of amino acids by

dissociation of one hydrogen atom at c-amino group.

Some amino acids and their amino acids residues/

+ortarLNa-c\o

H

amino acid

aminoacidresudue

NH^I J+'

CHzI

CHzI

CH:ICHz ^

"-* -J-.'1",/l\

H

lysineresidue

o-a'I

?,,9H, o

niN -g-.'(o

H

gluta m inats

ooa'oI

CHzICH: /.\H*l0viN-q-c\H

glutamineacid residue

NH-,1 'rrCHz

I

CHzI

CHzI

9H, oitltru*T-.-oH

Lysine

HTo/n-!{10

44

Terminology of peptides

Apolypeptide is a si.ngle Iinear chain of amino acid residues.Aprotein is one or more polypeptides contains more than about 50 amino acid residues long.An olrgopeptide or (simply) a peptide is a polypeptide less than 30-50 amino acid residues

long.A,dipeptide has two amino acid residues.Atripeptide has three amino acid residues-Atetrapeptide has four amino acid residues.Apenfapepfr'de has five amino acid residues.An ocfapepfide has eight amino acid residues.AnonapepfiUe has nine amino acid residues .Adecapepfide has ten amino acid residues.Acyclic peptide has the amino acid residues arranged into closed ring. ln this case the

peptide have not C- and N-terminals.

Linear tetrapeptyde and cyclic tetrapeptyde

Rlo Ho R3o H*H,N-8-A- N-[-8-* 8-_8-*-8- (nlll,lltr'\H HR' r{H Ii{+ o'\)

N-term inalamino acid

R,P HIc-t-N-c'/t tI\

/il H r..\H-bi C:O_I H. IC-O -N\H o N/\7^ fl t/C-N-C-C*/ ,! ,i

\-) r-C-terrn inalarn ino ac id

Linear peptide

Cyclic peptide

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Alanineseri ne and

?HI

CHs O CHz 11I '/i I - rrwHsN -? --cl -?--c \o'

HHHAla Ser Ser'

Seri n alan in e

Ala

Aanirieserine

The name and properties of peptide depends upon the sequence of amino acid residues inpeptide chain.

seri nalanine -

two different peptidesOH

I

?*' ,P ?*' ,,o*HsN-?-cl-?-c-o

HHH

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iBiological active Peptides

Glutathion -

tripep(ide formed with three amino acid residues: glutaminate, cysteineand glycine. The bonding between Gly and Cys is non-typical in peptid-es' This bond istorm-eO by y-carboxylic iroup of Glu instead the a'carboxylic group. Glutathion existsin two form; reduced and oxidized.

y-Glu ?f GIYBg) :$)t-/'

i'-Glu CYs GIY

SHIHrC\ ? ,-O

o.. /)-?-c-T -cHz-c-o-.C, H H H?*' cys

+ CHri ,oHaN

-?-61_o_H

Giv

2H

y-Glu

2H

y-Glu

A ^ ^t -giutarnaiecysteinegl-vcine

B - glr-riaihion redr-tce'd

,-\ eh r*^*$i^)- r'\vir'li-za.{-J y trr lca Ll I is.'l I \J-l\ iuia v \,t

Glv

y-Glu Gly

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BiologicallY active PePtides

Kini ns: kalidin (dekapeptyd). Lys-Arg-Pro-Gly'Phe'Ser'Pro'Phe'Arg and

bradyki ni n (nanopeptyd) : Arg-P ro-Gly-Phe-Ser-Pro-Phe'Arg differ only by one ami noacid (Lys)- tneyinUuce vaiodilatition (widening of-blqod vessels) and contraction ofsmooth muscles in digestive system.

Agniotensin I (decapeptide) - Asp-Arg-Val-Tyr-lle-His-Pro-Phe-His-Leu. Angiotensin I iscJnverted to angiotensin ll' (octapeptiue) through removal of two C'terminal residues (His'Leu). Angiotensin ll increases blood pressure by stimulating contraction of smooth musclesin biood vessels and regulates synthesis and releasipg of different hormones.

Enkefalins (pentapeptides)found in brain and their action is similar opioid alkaloids. Theanalgesic (painkilieri effects of enkefalins are due to decreased perception of pain,decreased reaction to pain as rryellas increased pain tolerance. Two more known

neurotransmitters, Mei-enkefalin and Leu-enkefatin, differ only by one amino acid (Met, andLeu, respectivelY).

Met-en kefali n - Tyr'G Iy'G ly-Phe'Met

Leu-[ kefali n - Tyr'Gly-G ly'Phe'Leu

C

9v=,'ffiilt'.S.,'

I

cys

4q

tsiolog ically active peptides

Endorphins ("endogenous morphrhe")are endogenous opioid peptides that function asneurotransmitters and are found in brain (pituitary gland and hypothalamus ) They haveanalgesic (painkiller) effects.Endorphin-cr- (heksadekapeptyd)

- Tyr-Gly-Gly-Phe-Met-Thr-Ser-Gln-Lys-Ser-Gln-Thr-Pro-Leu-

Val-Thr.

Endophirn-B contains 31 amino acids residues. lts fragment started from N-terminal contains16 amino acid residues and has sequence similar as in endorphirin-c .

Endorphin-y contains 27 amino acids residues with sequence similar to endorphinfin-p without 4amino acid residues bonded to C-terminal.

All endorphins have a common precursor - lipotropin-F, a 91 amino acid residues polipeptyde.

ln humans, o.endorphin, B-endorphin, y-endorphin, and met-enkephalin are all possiblefragments of B-lipotropin.

50

Other peptidesOxytocin is best known for roles in female reproduction: It is released in large amounts

after distension of the cervix and uterus during labor, and facilitating birth and breastfeeding.Vasopressin controls the reabsorption of molecules in kidneys by affecting the tissue'spermeability. lt also increases arterial blood pressure. It plays a key role in regulation of water,glucose, and salts in the blood. They both are nonapeptides and differ by two amino acids residues.Oxytocin and vasopressin are the only known hormones released by the human posterior pituitarygland to act at a distance.

oxytocin

\/\4 s/Cy? -Asnl,--..?ro-' leu:-61y

.3 ..2 ; 1

\, ,/Cys__--Asnt..-..?*..,lvs;gtv

(cont.)

9v.I

S

.8,'- Tyr

-

.Cys- Tyr/ e 8\ -'.s : zllejI'lt.ttS oGln

S

Q

/ Other peptides (cont.)Carnithine (B-alanylhistidine) i anserine (p-alanyl-N-methylhistidine) are found !nmuscles.

oil Tot/t T .,o*HuN

-cHzoil

HsN -CHz-CH 2-C -N-? -C \O-

CHzII

I

/-t't\r/H

-c H2-c-N -?-".o-CHzl.{'\xu.\//N,,

H,

carniti re ansen ne

Assurning, that polypeptides contains, up to 100 amino acids residues, to peptidesbelong also some hormones (parathyroid hormone, calcitonin, glucagon, insulin,adrenocorticotropic hormone, gastrin, secretin and cholecystokinin). ln human bodyexist many peptides

- proteins degradation products, They are intermediate metabolites

in protein degradation processes. Some of them are secreted by kidneys.

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