Shuxing Zhang, Ying Wong S, Siahaan Teruna J, Jois Seetharama D S
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Peptides. 2003 Jun;24(6):827-35. doi: 10.1016/s0196-9781(03)00170-0.
Cell-adhesion molecules are critical for immune response. It is well known that the inhibition of adhesion is very effective in immunotherapy and that the peptides derived from leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1) modulate cell-adhesion interaction. The three-dimensional structure of a cyclic peptide, Cyclo(1,12)Pen(1)-Asp(2)-Leu(3)-Ser(4)-Tyr(5)-Ser(6)-Leu(7)-Asp(8)-Asp(9)-Leu(10)-Arg(11)-Cys(12) (cLBEL) derived from the beta subunit of LFA-1 which is known to modulate homotypic T-cell-adhesion process has been studied using NMR, CD and molecular dynamics (MD) simulation. The peptide exhibits two possible conformations in solution. Structure I has a conformation with two consecutive beta-turns involving residues Tyr(5)-Ser(6)-Leu(7)-Asp(8) and Asp(9)-Leu(10)-Arg(11)-Cys(12). Structure II has a beta-turn at Tyr(5)-Ser(6)-Leu(7)-Asp(8) and forms a beta-hairpin type of conformation.
细胞黏附分子对免疫反应至关重要。众所周知，在免疫治疗中抑制黏附非常有效，并且源自白细胞功能相关抗原（LFA-1）和细胞间黏附分子（ICAM-1）的肽可调节细胞黏附相互作用。已使用核磁共振（NMR）、圆二色光谱（CD）和分子动力学（MD）模拟研究了一种环状肽Cyclo(1,12)Pen(1)-Asp(2)-Leu(3)-Ser(4)-Tyr(5)-Ser(6)-Leu(7)-Asp(8)-Asp(9)-Leu(10)-Arg(11)-Cys(12)（cLBEL）的三维结构，该肽源自LFA-1的β亚基，已知其可调节同型T细胞黏附过程。该肽在溶液中呈现两种可能的构象。结构I具有一种构象，其中包含由Tyr(5)-Ser(6)-Leu(7)-Asp(8)和Asp(9)-Leu(10)-Arg(11)-Cys(12)组成的两个连续β-转角。结构II在Tyr(5)-Ser(6)-Leu(7)-Asp(8)处有一个β-转角，并形成一种β-发夹型构象。
