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多肽合成中困难序列的缩合研究进展(6)

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116

药学学报Acta

PharmaceuticaSinica

2007,42(2):111—117

yields

fortherapidSPPS.using

Boc—aminoacid

derivatives,of

CGRP(human一Ⅱ.caleitonin

gene—

relatedpeptide)(8—37).They

observed

that

coupling

yields

are

highly

dependent

on

thesolventused.Maximumresinsolvationoccurred

with

NMP.

NMP—DMSO(8:2)andDMSO.Inefficientsolvationof

the

peptide—resin

occurred

with

these

solvents

and

resultedinpoorsyntheseswithaveragecouplingyieldsof78.1。88.9and

91.8%.respectively.Superior

peptide—resin

solvationwas

obtainedusing

DMA

(dimethylacetamide)

and

DMF,

resultingin

significantlyhigheraveragecouplingyieldsof98.0and

2).

Average

couplingyieldsforthe

synthesisof

Solventsystem

Avg.coupling

yield/%

DMF

provided

themosteffective

peptide—resinand

was

theonly

solventfrom

whichCGRP

obtained

as

singlemajorproductinthe

cleavedmaterial.Itshouldpointout

thatunderconditions

the

peptidyl—resin

has

differentresponses

even

inthe

same

solvent.

solventnot

onlywiththechangeofchainlengthbutalso

withthe

alternation

of

stages

ineach

syntheticcircle.such

as

the

deprotecting

and

couplingsolvents,isnecessary

for

the

enhancement

of

coupling

Thus,the

success

of

SPPSisoften

dependent

solvationoftheresinandthegrowingresin—bound

chain.Theuse

ofnewsupports

thatincreaseseparation

and

peptide

chain

solvation

is

CLPSER(cross—linked

polystyrene—

acrylate

resin)。3“showed

excellent

in

broadrangeofsolventsused

in

SPPS.newresinwascomparedwithcommercialsupportsas

MerrifieldandSheppardresinsbysynthesizing

acylcarrier

protein(65—74)fragment

underthe

experimental

conditions.HPLC

(high—

liquid

chromatography)profiles

revealed

highefficiencyofthenewlydevelopedsupport.CM

(polyethylene

glyc01)一based

resin,performing

excellentlyfor

the

preparationofhydrophobic,highly

structured,andpoly—Argpeptides,ascomparedtoPS

(polystyrene)resins.Themechanis …… 此处隐藏:1945字,全部文档内容请下载后查看。喜欢就下载吧 ……

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