Supramolecular Science 4 (1997) 449453 ‘1, 1997 Elsevier Science Ltd Printed in Great Britain. All rights reserved ELSEVIER PII:SO968-5677(97)00044-g 0968-5677/97/$17.00 Physicochemical study of laminin-related peptides Nliria Rubib, Montse Pujol*, Montse Muiioz and M. Asunci6n Alsina Unitat de Fisicoquimica, Facultat de FarmBicia, Avgda Joan XXIII s/n, 08028 Barcelona, Spain and Isabel Haro and Francesca Reig Departament de Pkptids, CID-CSIC, C/Jordi Girona Salgado 18-26, 08034 Barcelona, Spain (Received 14 *September 1996; revised 11 January 1997) Four peptide analogues related to the active sequence YIGSR of laminin have been synthesised. The synthesis and chemical characterisation of the peptides are described. Physicochemical properties of these peptides such as surface activity, spreadability, monolayer formation, as well as their interaction with lipid monolayers and bilayers, have been studied by using Langmuir-Blodgett films and liposomes as membrane models. In spite of their good water solubility, these peptides are able to form stable monolayers at the air/water interface and to insert into lipid monolayers. The interaction with bilayers is soft; they are not able to induce the leakage of entrapped CF nor to modify the microviscosity of bilayers in general. Thus in these models electrostatic forces apparently do not play an important role, as we expected previously according to the electrical charge of bilayers, markers and peptides. 0 1997 Elsevier Science Ltd. All rights reserved. (Keywords: laminin; lipid monolayer; fluorescent probes) INTRODUCTION MATERIALS AND METHODS Since their first description, adhesion molecules have been studied extensively as potential carriers and targetting effecters for cytostatics in the treatment of cancer”2. Laminin is olne of the most important molecules related to adhesion and the spreading of metastases. Several regions in this large glycoprotein have been associated with receptor binding and, in consequence, can be considered as active to interact with tumour cells where laminin receptors are overexpressed3*4. It has .been clearly established that these proteins and their corresponding active fragments (YIGSR, for instance) act on specific receptors located on the surface of tumour and metastasic cells. Chemicals According to the model of Sargent and Schwyzer’ the amphipathic domain of the lipid bilayer acts as a catalyst, facilitating subsequent interaction with specific receptors in the resulting two-dimensional plane. In this context there is evidence that binding to lipids is required for the activity of opioid peptides6, signal peptides and many peptide hormoness. Dipalmitoyl phosphatidylcholine (DPPC), phosphatidylglycerol (PG) and stearylamine (SA) were purchased from Sigma Chemicals; their purity, as checked by thin layer chromatography, was shown to be > 99%. Sodium anilinonaphthalenesulfonate (ANS), 1,6-diphenyl- 1,3,5,-hexatriene (DPH) and 1-[4-(trimethyl- ammonio)phenyl-6-phenyl- 1,3,5-hexatriene (TMA-DPH) were supplied by Sigma. Carboxyfluorescein (CF) from Eastman Kodak was purified by column chromatography as described by Weinstein et a1.9. Chloroform and methanol were from Merck. Water for the Langmuir film balance was distilled twice over permanganate and passed through a Milli-Q filtration system. Its resistivity was always > 18MRcn-’ and pH was 5.M; it was always freshly prepared. Synthesis of peptides *To whom correspondence should be addressed The synthesis of the four peptides used in this work was carried out manually on the solid phase using a p- methylbenzhydrylamine (p-MBHA) resin and 4-(2’,4’- dimethoxyphenyl-Fmoc-aminomethyl)-phenoxyacetamido (AM) linker in order to obtain an amide group on the SUPRAMOLECULAR SCIENCE Volume 4 Numbers 3-4 1997 449