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多肽合成中困难序列的缩合研究进展(2)

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非常详细的综述性文章

药学学报Acta

PharmaceuticaSinica

2007,42(2):111—117

available

impact

to

minimize

oreven

abolishthe

negative

alsosuccessfully

applied

to

theassemblyofpeptides

ofthe

these

use

sequencesduringsynthesis.These

reagents。…,

in

containingseveralsecondaryandhinderedamines.2

ReasonableroutesforfragmentscouplingSegmentscondensationis

synthesis

of

long

sequence

an

includewhich

ofgive

powerful

acylating

protocolssignificant

increasethefor

importantwayforthepeptide.

“Difficult

efficiencyofpeptide

chain

assembly,especially

‘‘difficultsequences”.Thepopularityofuroniumbasedcouplingreagents

for

peptide

synthesis

has

increasedthatproved

as

sequences”may

becircumventedbyadequatedefinition

correct

ofsegmentand

For

choiceofcondensationsite[9|.

can

significantly(Figure1).Certain

to

sequences

longpeptidessynthesis,thetargetpeptide

into

several

protected

were

or

be

bemore

difficult

to

synthesize,such

BoPrPdividedcarboxyl

fragments.Those

chosen

which

amino

(bovine

Prion

Protein)(90—200),were

successfullycomponents

Gly

to

generally

as

preparedusing

combinationofthe

highlyactivated

usuallycontainacid.in

order

Pro

the

C—terminal

couplingreagent

1,

HATU(O一(7-azabenzotrizole一1一y1)一

hexanuorophosphate)

total

of

and

et

minimizethe

possibleracemization

1,3,3一tetramethyluronium

duringtheshortfragmentssynthesis,andthen,口一sheet

was

not

(Figure

1)

t-Boc

(tert.butyloxycarbonyl)

synthesis

the

tendency

to

beformedinthe

produced

chemistry[3].Wu

al[7]reported

longer

intermediate㈨.In

should

otherword,whenthelonger

performed,the

at

human理一defensins4,5,and6,usingthe

optimizedneutraliza—

fragmentscondensationreactionswerePro

residue

be,if

of

DIEA(N,N—diisopropylethylamine)in

tetramethyluronium

activationreport

situ

possibly,locatedC—terminal

in

the

tion/HBTU(2一(1H—benzotriazol一1一y1)一1,1,3,3一

hexanuorophosphate)(Figure …… 此处隐藏:1717字,全部文档内容请下载后查看。喜欢就下载吧 ……

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