CAJ | 학술논문

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。
장담고순분자통과1개반광안산측련류미건화1개β-병안산련접비인입도소설계적비천연HR서렬항HIV융합활성다태적C단화N단，합성료여천연C태서렬동원성흔저적비천연서렬적류태항HIV융합분자，이고찰담고순수식대비천연HR서렬활성적영향，탐토극복내약성적신사로。생물활성평개결과표명，담고순여HR태C단결합물억제HIV융합활성현저제고，이련접도N단적서렬칙완전실거료항병독활성，표명소설계적비천연서렬학실구유여천연서렬유사적작용궤제。
As addition of 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 β-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.