Potent peptide dimers

Dutta AS, Crowther M, Gormley JJ, et al. Potent cyclic monomeric and dimeric peptide inhibitors of VLA-4 (a4Pi integrinj-mediated cell adhesion based on the Ile-Leu-Asp-Val tetrapeptide. ] Pept Sci 2000 6 321M1. 

By carefully adjusting the distances between two sialoside residues in a number of divalent clusters. Click and Knowles [105] have obtained dimer 104 having the two sialic acid 5.7 nm apart. Compound 104 was 100-fold more potent than methyl a-sialoside (Neu5Aca2Me) in influenza virus inhibitions and 500-fold more potent in the case of polyomia virus. Alternatively, sialyl-a-(2,6)-/3-LacNAc dimers (105) branched at different positions of synthetic peptides, including compact glycine-rich and helical proline-rich peptides, afforded clusters which were only 8- and 4-fold more potent, respectively, than the corresponding monovalent trisaccharide [106]. 

Proteins and the larger polypeptides of molecular weight greater than about 5000 will readily stimulate a potent immune response. Many may exist in dimer or polymer form, either naturally or as a result of minor denaturation during purification, and this may increase their immunogenicity (major denaturation may be associated with loss of native antigenic characteristics, however, and should be avoided). The smaller the peptide... 

A common feature of nearly all X-ray crystal complexes between HIVPR and peptide-derived peptidomimetic inhibitors (PPIs) is the presence of a tetracoordinated structural water molecule tightly bound between the inhibitor molecule and the flexible beta strands or flaps of the HIVPR dimer. This ubiquitous water molecule accepts two hydrogen bonds from backbone amide bonds of flap residues IleSO and IleSO and donates two hydrogen bonds to suitable acceptors, typically carbonyl groups, which flank the transition state isostere of the peptide mimetic inhibitor (Fig. 3a) [31]. Potent... 

---