Synthesis of peptide-cellulose conjugate mediated by a soluble cellulose derivative having β-Ala esters
Synthesis of peptide-cellulose conjugate mediated by a soluble cellulose derivative having β-Ala esters
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由具有β-丙氨酸酯的可溶性纤维素衍生物介导的肽-纤维素缀合物的合成
DOI：
10.1016/j.ijbiomac.2012.11.004
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发表时间：
2013
影响因子：
8.2
通讯作者：
Masakazu Hachisu and Jun Araki
中科院分区：
文献类型：
--
作者：
Kousaku Ohkawa;Mikiko Mishibayashi;Kesavan Devarayan;Masakazu Hachisu and Jun Araki
研究了纤维素的衍生化以获得随后缀合反应的溶解度。用羰基二咪唑将Nβ-Boc-β-Ala引入到母体纤维素中。纤维素羟基的取代度为49%。随后在三氟乙酸（TFA）中除去Boc，得到β-Ala-纤维素·TFA盐。通过9步延伸反应合成了一个保护的六肽Boc-Ser（Bzl）-Gly-Tyr（Bzl）-Ser（Bzl）-Gly-Lys（Z），并在均相二甲基亚砜溶液中用1-乙基-3-（3-二甲氨基丙基）碳二亚胺盐酸盐将其C端羧基与β-Ala-纤维素偶联，以保证Nβ选择性酰化。对于1.0当量摩尔的保护肽进料，保护肽对β-Ala-纤维素的β-氨基的取代度（DS%（/NH 2））为52%，并且在N-羟基琥珀酰亚胺存在下，DS%（/NH 2）增加至61%。在4.0当量摩尔进料下，观察到几乎定量的缀合，DS%（/NH 2）=98- 99%。使用茴香硫醚-TFA对缀合物进行脱保护导致Boc、Tyr上的Bzl和Lys上的Z的完全去除，而Ser上极痕量的Bzl似乎未被切割。
A derivatization of cellulose was investigated for gaining up the solubility for subsequent conjugation reaction. Nβ-Boc-β-Ala, was introduced to the parent cellulose using carbonyl diimidazole. Degree of substitution towards the cellulose hydroxyls was 49%. Subsequent removal of Boc in trifluoroacetic acid (TFA) yielded β-Ala-cellulose·TFA salt. A protected hexapeptide, Boc-Ser(Bzl)-Gly-Tyr(Bzl)-Ser(Bzl)-Gly-Lys(Z) was synthesized via 9 steps of peptide elongation, and the C-end carboxyl groups of the peptide was coupled with the β-Ala-cellulose in a homogenous dimethyl sulfoxide solution, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide monohydrochloride to ensure the Nβ-selective acylation. The degree of substitution of the protected peptide towards the β-amino groups of β-Ala-cellulose (DS%(/NH2)) was 52% for 1.0eq.mol of the protected peptide feed, and in the presence of N-hydroxysuccinimide, DS%(/NH2) was increased to 61%. At 4.0eq.mol feed, almost quantitative conjugation was observed as DS%(/NH2)=98–99%. Deprotection of the conjugate using thioanisole–TFA resulted in complete removal of Boc, Bzl on Tyr, and Z on Lys, while a very trace amount of Bzl on Ser seemed to be left uncleaved.