多肽合成中困难序列的缩合研究进展(5)
时间:2025-03-10
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
a
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
a
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