多肽合成中困难序列的缩合研究进展(5)

时间:2025-03-10

非常详细的综述性文章

HANXiang.etal:Recent

progress

intheimprovementofthecouplingefficiencyof‘‘difficultsequences’’in

peptidesynthesis

methane)一polarsolvents

clearly

indicatedthatthe

solubilityofpeptides,such

as

Boc—Leu9-OBzl,with

卢-sheet

structure

in

organicsolventswasindependentof

thepolarityofsolventsbutwasstronglydependenton

theirhydrogen

donating

and

accepting

ability.The

hydrogenbonding

between

peptide(P)and

solvents

(S)suchas(P)N—H…O=C(S),(P)N—H…O=S(S),(P)N—H…O=P(S),and(P)C=O…H—O(S)

shouldbethebase

on

which

8.sheetstructureis

formed.Inthesubsequentstudy.Cilli

et

al[24]

demonstrate

that

the

8-sheet

structure—disrupting

potentialofhydrogen -donorand--acceptorsolventsisingoodrelationship

with

theirelectron—acceptor

and

—donor

numbers(ANand

DN)respectively.They

foundthattheANorderofhydrogendonorsolventsisarranged

as:HFIP(hexanuoroisopropan01)

>PhOH

(phen01)>TFE(2,2,2-trifluoroethan01)>AcOH

(aceticacid)>MeOH(methan01)>EtOH(ethan01)>

nBuOH(凡一butan01)>iPrOH(isopropan01),and

in

theDN

order

of

hydrogen

acceptor

solvents,HMPA

(hexamethylphosphoramide)>DMSO>TMP(1,1,

1一tri(hydroxymethyl)propane)>NMP(N—methyl一2一

pyrrolidone)>DMF(N,N—dimethylformamide),and

thetendenciesofANandDNwerelarger,theirp—sheet

structure

disrupting

potential

become

higher.Among

the

solvent

systemstested[22I.amixture

of

TFE

or

HFIPand

TCM(trichloromethane)or

DCMwasfound

to

bemostpowerfulfordissolvingthesparingly—soluble

protectedpeptides.

It

is

obvious

thatcombinationsof

homogenous

solvents(all

are

AN

or

DN)areonlysuitable

for

solubility

improvement,and

those

ofheterogeneous

(AN+DN)oneswould

not

beeffective.Asa

matter

offact,theprincipleof

usinghomogeneous

mixed

solventsforsolubility

improvingwas

employed

years

beforein

the

synthesis

of

BovinePancreaticRNase

A[25|.TheeffectofchaotropicsaltsPossibly

chaotropic

salts[26j

decrease

secondary

formationin

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