多肽合成中困难序列的缩合研究进展

发布时间:2021-06-08

非常详细的综述性文章

药学学报Acta

PharmaceuticaSinica

2007,42(2):111—117

.111.

综述

Recentprogressinthe

improvementofthecouplingefficiency

of“difficult

sequences"inpeptidesynthesis

HANXiang,WANGDe—xin+

(InstituteofMateriaMedica,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege,Beijing100050,China)

Abstract:EventhoughchemistryisnOWinplacethatpotentiallyallowshighcouplingefficiencies

beattained,successfulcouplingisusuallyinpeptide

synthesis.Somefactors

that

to

challengewhenSO—called‘‘difficultsequences”isenc!ountered

have

been

discussed

and

related

affectthecouplingefficiency

methodstoovercomethoseobstacleshavebeenintroducedinpresentreview.All

suggestionsproposedhere

are

valuableandalsofeasibleto

improvethe

couplingcompletenessinbothliquid..phase

Ot

solid..phase

peptidesynthesis.

Keywords:peptidesynthesis;couplingefficiency;difficultsequences;口.structureofpeptide

CLC

number:R916Documentcode:A

Article

ID:0513—4870(2007)02一0111—07

多肽合成中“困难序列"的缩合研究进展

香,王德心+

(中国医学科学院、中国协和医科大学药物研究所,北京100050)

摘要:化学学科发展至今拥有极强的能力来获得高的合成效率,但是在多肽合成中“困难序列”的存在仍然成为成功缩合的巨大挑战。本文综述了影响多肽缩合效率的因素以及提高“困难序歹旷缩合效率的有效方法。所述方法均简便易行,适用于多肽的固相合成或液相合成。

关键词:多肽合成;缩合效率;困难序列;口一构象

The

long

phenomenon

of“difficultin

their

sequences”has

to

residuesfromdue

the

to

resinexistintra

or

interchain

frustratedchemistsefforts

assemble

or

aggregationto

hydrogenbonds,producingdifficulty

the

occurrence

peptidescontainingsuch

sequences

bysolid

liquidcouplingreaction。“.Although

and

phasesynthesisprotocols。1’….Theconventionalcouplingmethods,such

as

severity

of“difficult

sequences”cannot

bepredicted

activeesterand

acid—anhydride

are

withconfidence,itisgenerallythoughtthatarisesfromthe

intermolecular

into

association

sometimesfailed

to

overtomethatobstacle[3I.The

not

use

ofresin.bound

structures

peptideduringthe

N—

ofnewcouplingreagentissynthesis,because

reactantsin

or

alwaysfruitfulinpeptidefrom

the

insolubility

of

chains

extended卢一sheet

assembly。“.Such

inaccessible

to

type

troubles

sequentialterminalgettingthe

structureled

thepoorswellingstateofpolymersupport

phasepeptidesynthesis)gofarbeyond

into

beacylated.Therefore,

to

SPPS(solid

Some

clearunderstandingofthefactorsthatlead

of

secondary

effective

structure

theabilityofcouplingreagent.

sequences

formationin

certain

inthe

lengthrange

of5—15

sequences

andadoptingmeasurestoimprove

thecouplingefficiencyshouldbeveryvaluable.

Received

date:2006-06-01.

item:National

Natural

Science

Foundation

of

China

The

employmentofhighlyefficient

coupling

Foundation

methods

Overcomingthe

sequences”hasbeen(30572244).

+Correspondingauthor

Tel:86—10—63165251.Fax:86—10—63017757,

phenomenonknown

as“di岱cult

majortaskinpeptidesynthesis

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