Structure-Based Rational Design of -Hairpin Peptides from Discontinuous Epitopes of Cluster of Differentiation 2 (CD2
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- 作者：Jining Liu ; Cheng Li ; Shao Ke ; Seetharama D. Satyanarayanajois
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：August 23, 2007
- 年：2007
- 卷：50
- 期：17
- 页码：4038 - 4047
- 全文大小：418K
- 年卷期：v.50,no.17(August 23, 2007)
- ISSN：1520-4804
文摘
Modulation or inhibition of interaction of cluster of differentiation (CD) adhesion molecules CD2-CD58has been shown to be therapeutically useful. The analysis of the crystal structure of CD2 complexed withCD58 was carried out to define the epitopes that are important for the interaction of the two proteins. Thecrystal structure of CD2 indicated that the interaction surface of CD2 with CD58 has two 
-strand structures(F and C strands) with charged residues. On the basis of the crystal structure of the complex CD2-CD58,we have designed -hairpin peptides from the -strand region of CD2 by conjugating the discontinuoussequences in the protein. The peptides were modeled by molecular dynamics simulation, and their inhibitoryactivities were evaluated in vitro using two heterotypic cell adhesion assays, E-rosetting and lymphocyte-epithelial cell adhesion assays. Results indicated that 12- and 14-residue conjugate cyclic peptides cKS12and cDD14 exhibited 60% and 50% inhibition activity, respectively, at 90 
M.
-strand structures(F and C strands) with charged residues. On the basis of the crystal structure of the complex CD2-CD58,we have designed -hairpin peptides from the -strand region of CD2 by conjugating the discontinuoussequences in the protein. The peptides were modeled by molecular dynamics simulation, and their inhibitoryactivities were evaluated in vitro using two heterotypic cell adhesion assays, E-rosetting and lymphocyte-epithelial cell adhesion assays. Results indicated that 12- and 14-residue conjugate cyclic peptides cKS12and cDD14 exhibited 60% and 50% inhibition activity, respectively, at 90 M.