摘要
将胆固醇分子通过1个半胱氨酸侧链硫醚键和1个β-丙氨酸连接臂引入到所设计的非天然HR序列抗HIV融合活性多肽的C端和N端,合成了与天然C肽序列同源性很低的非天然序列的类肽抗HIV融合分子,以考察胆固醇修饰对非天然HR序列活性的影响,探讨克服耐药性的新思路.生物活性评价结果表明,胆固醇与HR肽C端结合物抑制HIV融合活性显著提高,而连接到N端的序列则完全失去了抗病毒活性,表明所设计的非天然序列确实具有与天然序列类似的作用机制.
As addition ot a cholesterol group to nature peptide fusion inhibitor can dramatically increase its antiviral potency, we designed and synthesized a series of cholesterol conjugated artificial peptide with low sequence homologous from HIV-1 gp41 as HIV-1 fusion inhibitors. The cholesterol moiety was introduced into C- or N-terminal of the peptide through a thioether in cysteine side chain and a/3-alanine linker to study the effect of cholesterol modification to the activity of non-natural HR sequence and explore new method to over- come the problem of HIV drug resistance. Cell-cell fusion assays showed that the fusion inhibitory activity of the C-terminal cholesterol conjugated peptide was significantly increased, while the activity of N-terminal con- jugated peptide was completely lost, consistent with the reported peptide conjugation using native peptide sequence, indicated that the designed non-natural sequences had a similar mechanism of action with natural sequences. This work provided a useful base for further drug optimization and discovery of highly active non- natural peptide sequences.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2014年第12期2542-2546,共5页
Chemical Journal of Chinese Universities
基金
国家自然科学基金(批准号:81373266)
'重大新药创制'科技重大专项项目(批准号:2012ZX09301003)资助~~
关键词
HIV融合抑制剂
多肽
耐药性
非天然序列
HIV fusion inhibitor
Peptide
Drug resistance
Non-natural sequence
