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
a
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
韩
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
a
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
1
Foundation
of
China
The
employmentofhighlyefficient
coupling
Foundation
methods
Overcomingthe
sequences”hasbeen(30572244).
+Correspondingauthor
Tel:86—10—63165251.Fax:86—10—63017757,
phenomenonknown
a
as“di岱cult
majortaskinpeptidesynthesis