New analogues of laminin active fragment YIGSR: synthesis and biological activity in vitro and in vivo

Abstract

Eleven analogues of the laminin pentapeptide amide fragment Tyr-Ile-Gly-Ser-Arg-NH2 (YIGSR-NH2) corresponding to a B1 chain fragment of the glycoprotein laminin have been synthesized by the solid phase method, and their biological activity has been studied in vitro by a cell adhesion assay: all of them inhibited the adhesion of LLC tumor cells to laminin. The analogues were found to be more resistant to enzymatic degradation in human serum than YIGSR-NH2 itself. Analogue DatIGSHar-NH2 was selected for an experimental pulmonary metastasis assay in vivo: it had higher antimetastatic activity than YIGSR-NH2.

A cell adhesive peptide from tropoelastin promotes sequential cell attachment and spreading via distinct receptors

“…Features of these perturbing tyrosine and lysines in our tropoelastin-derived sequence are variously present in multiple ECM-binding ligands, such as the laminin-derived YIGSR and DYATLQLQEGRLHFMFDLG sequences [55][56][57], the GRKRK motif in tropoelastin, and the RKKH sequence derived from jararhagin, a hemorrahagic snake venom metalloproteinase. Features of these perturbing tyrosine and lysines in our tropoelastin-derived sequence are variously present in multiple ECM-binding ligands, such as the laminin-derived YIGSR and DYATLQLQEGRLHFMFDLG sequences [55][56][57], the GRKRK motif in tropoelastin, and the RKKH sequence derived from jararhagin, a hemorrahagic snake venom metalloproteinase.…”

“…Mutations were introduced into Peptide 302-322 to investigate the specific amino acids involved in mediating cellular interactions. Features of these perturbing tyrosine and lysines in our tropoelastin-derived sequence are variously present in multiple ECM-binding ligands, such as the laminin-derived YIGSR and DYATLQLQEGRLHFMFDLG sequences [55][56][57], the GRKRK motif in tropoelastin, and the RKKH sequence derived from jararhagin, a hemorrahagic snake venom metalloproteinase. Therefore, these residues in Peptide 302-322 were sequentially alanine-substituted to investigate their role in cell interactions (Fig.…”

Multi-responsive supramolecular hydrogels based on merocyanine–peptide conjugates

“…Encouraged by the success of MC-dipeptide hydrogelation, we proceeded to prepare SPI conjugates with a variety of bio-functional oligopeptides of 3-7 amino acids (Scheme 2). Among these oligopeptides, VPP is a milk casein derived tripeptide that modulates monocyte adhesion to vascular endothelium; 25 YSV is known as tyroservatide that inhibits tumor invasion and metastasis; 26 VYGGG exhibits inhibitory effects in binding the monoclonal antibody, 10 D 11 ; 27 IKVAV and YIGSR are small laminin peptides that promote neurite outgrowth; 28 Fig. 1 The generation and self-assembly of merocyanines from the reverse photochromism of spiropyrans.…”

Poster Session I Abstracts

“…Recent studies have demonstrated that helicity-enhancing substitutions yielded potent analogues of PTH(1-11) and PTH (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The role of -helicity on biological potency is well known.…”

“…We named these functional peptides that were hidden in protein structures as ''cryptides'' [2,3]. We also found that many cryptides activated other cells such as mast cells [4][5][6]. Here, we report the discovery of mitocryptide-2 (MCT-2), another type of neutrophilactivating cryptide from porcine heart.…”