扩展顺式-β-糖氨基酸的构象库：β-hGly基序在稳定的14螺旋中的容纳情况

Expanding the conformational pool of cis-beta-sugar amino acid: accommodation of beta-hGly motif in robust 14-helix.

作者信息

Chandrasekhar Srivari, Reddy Marepally Srinivasa, Babu Bathini Nagendra, Jagadeesh Bharatam, Prabhakar Anabathula, Jagannadh Bulusu

机构信息

Division of Organic Chemical Sciences, Indian Institute of Chemical Technology, Hyderabad 500 007, India.

出版信息

J Am Chem Soc. 2005 Jul 13;127(27):9664-5. doi: 10.1021/ja051014d.

DOI:10.1021/ja051014d

PMID:15998052

Abstract

Tendencies of forming stable helices of heterooligomers composed of alternating rigid cis-beta-sugar amino acid and flexible beta-hGly motifs have been investigated, using a combination of molecular mechanics, CD, FT-IR, and NMR techniques. The results show that the solution structures of these oligomers exist as robust right-handed 14-helices. Here, we examine the role of conformationally rigid cis-beta-sugar amino acid in preorganizing the conformation of beta-hGly to form the 14-helix. Our findings also show that a right-handed 14-helix can be formed with as few as four properly sequenced heterogeneous residues. These results represent the expansion of the conformational pool of sugar amino acid in the design of well-folded 14-helices, which can be used to develop beta-peptides endowed with biological activity.

摘要

利用分子力学、圆二色光谱（CD）、傅里叶变换红外光谱（FT-IR）和核磁共振（NMR）技术相结合的方法，研究了由交替的刚性顺式-β-糖氨基酸和柔性β-hGly基序组成的异源寡聚体形成稳定螺旋的趋势。结果表明，这些寡聚体的溶液结构以稳健的右手14螺旋形式存在。在此，我们研究了构象刚性的顺式-β-糖氨基酸在预组织β-hGly的构象以形成14螺旋中的作用。我们的研究结果还表明，只需四个正确排序的异质残基就能形成右手14螺旋。这些结果代表了在设计折叠良好的14螺旋时糖氨基酸构象库的扩展，可用于开发具有生物活性的β-肽。