Seryl-lysine

The cell adhesion molecule, N-cadherin plays a pivotal role in many biological and disease processes. Drugs that modulate N-cadherin function should therefore be useful therapeutic agents. We have used phage display technology to identify amino acid sequences capable of binding to N-cadherin. All of these sequences harbor a Trp residue in the second position from the N-terminus. A synthetic linear peptide containing one of these sequences, H-SWTLYTPSGQSK-NH(2) was found to bind a chimeric protein composed of the N-cadherin ectodomain fused to the immunoglobulin G1 Fc fragment with an affinity (K(D)) of 10.7microM, as determined by surface plasmon resonance. It also blocked the aggregation of beads coated with this chimeric protein. Furthermore, this peptide disrupted adhesion and tube formation by N-cadherin-expressing human umbilical vein endothelial cells in vitro. These observations suggest that N-cadherin antagonists have the potential of serving as anti-angiogenic agents. The peptide, H-SWTLYTPSGQSK-NH(2) should prove useful for studies designed to evaluate N-cadherin function in various biological processes.

Monoclonal antibodies were raised against a synthetic NH2-terminal myristoyl tetrapeptide (N-myristoyl-Gly-Ser-Ser-Lys) which is characteristic of an NH2-terminal portion of pp60src, the transforming protein of src-oncogene. The antibody reacted with the albumin conjugated with both the N-myristoyl and N-lauroyl-tetrapeptides, but concentrations at which 50% of the immunoreaction was inhibited were 5 pmol for the N-myristoyl and 830 pmol for N-lauroyl tetrapeptidyl albumin. On the other hand, N-palmitoyl tetrapeptidyl and underivatized albumin, and Gly-Ser-Ser-Lys-Ser-Lys-Pro-Lys octapeptide had no effects. These results suggest a high affinity of the antibody for an N-myristoyl-Gly-Ser-Ser-Lys moiety. src-Oncogene products in Rous sarcoma virus-transformed cells and human colon carcinoma tumor cells were selectively identified as myristoylated pp60src by immunoprecipitation analyses with the antibody.

Tripalmitoyl-S-glycerylcysteinyl lipopeptides are B-cell and macrophage activating and may be used as low molecular weight immunogens of considerable potency and even as vaccines when conjugated with suitable epitopic structures. Selected lipopeptides carrying single Dnp haptens were found to evoke mild passive cutaneous anaphylaxis in guinea pigs sensitized against Dnp. The reactions were observed after intravenous injection whereas intradermally applied antigen was negative. The anaphylactogenicity seems unrelated to micelle or aggregate formation of the insoluble peptides which require lecithin additions as well as sonication to become solubilized. The dinitrophenylated lipopeptide tripalmitoyl-S-glyceryl-cysteinyl-seryl-lysine produced toxic reactions which were not observed with the lipopeptide devoid of Dnp. Dinitrophenylated tripalmitoyl-S-glycerylcysteiny-1,6-diaminohexane and tripalmitoyl-S-glyceryl-cysteinyl-lysine did not show these toxic reactions.