Elastin is an extracellular matrix protein responsible for the elastic properties of organs and tissues, the elastic properties being conferred to the protein by the presence of elastic fibers. In the perspective of producing tailor-made biomaterials of potential interest in nanotechnology and biotechnology fields, we report a study on an elastin-derived polypeptide. The choice of the polypeptide sequence encoded by exon 6 of Human Tropoelastin Gene is dictated by the peculiar sequence of the polypeptide. As a matter of fact, analogously to elastin, it is constituted of a hydrophobic region (GLGAFPAVTFPGALVPGG) and of a more hydrophilic region rich of lysine and alanine residues (VADAAAAYKAAKA). The role played by the two different regions in triggering the adoption of beta-turn and beta-sheet conformations is herein discussed and demonstrated to be crucial for the self-aggregation properties of the polypeptide. 1. Introduction The natural extracellular matrix (ECM) has been, over the years, a source of inspiration for the design and the production of biomaterials of potential interest as scaffolds in tissue engineering [1, 2]. The propensity to self-aggregate, typical of the proteins contained in ECM, into nanostructured fibers and fibrils, makes it strongly attractive. Over the last years, there has been a remarkable progress in the synthesis of ECM protein-inspired polypeptides. Elastin is the ECM protein responsible for the elasticity of organs and tissues such as lungs, skin, and arteries, the elastic properties being conferred on elastin by the presence of fibers [3]. The propensity to self-aggregate was also demonstrated for some soluble elastin derivatives such as -elastin and -elastin and for some short-synthetic peptides [4]. More recently, long elastin-derived polypeptides obtained both by DNA recombinant technologies and by chemical synthesis were investigated and demonstrated to be able to self-aggregate into fibers and fibrils, analogously to the entire protein [5, 6]. In this context, a crucial role is played by the peculiar sequence of the polypeptide [7]. The outstanding mechanical properties of elastin are due to the regular alternance of hydrophobic regions, rich in glycine, alanine, valine, and leucine, and of hydrophilic domains rich in alanine and lysine residues [7]. The hydrophobic sequences give elasticity while the hydrophilic [8] ones confer to the protein resistance to rupture and fatigue. As a matter of fact, the hydrophilic domains are involved in the formation of covalent cross-links occurring between adjacent molecules
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