Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Int J Mol Sci. 2021 Mar 3;22(5):2528. doi: 10.3390/ijms22052528.
Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the -terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.
超分子肽水凝胶由于其在各种生物医学应用中的潜力而受到越来越多的关注。它们的物理性质与细胞外基质 (ECM) 相似，这是它们在专门细胞培养、组织工程、皮肤再生和伤口愈合等方面应用的关键。这些水凝胶的结构通常由二肽或三肽组成，在 - 末端用疏水性芳香基团（如 Fmoc 或萘基）封端。尽管这些肽缀合物相对于其他类型的凝胶剂（如交联聚合物）具有优势，但它们通常存在对内源性蛋白酶的水解特别敏感的局限性。克服这一障碍的一种已报道策略是使用肽模拟策略，其中天然氨基酸被非蛋白质类似物（如 D-氨基酸、β-氨基酸或脱氢氨基酸）取代。这种肽通常具有更大的抗酶水解能力。含有脱氢氨基酸的肽，即脱氢肽，特别有趣，因为双键的存在也会对肽主链引入构象约束，导致肽的二级结构发生（通常可预测的）变化。本文综述了肽水凝胶和相关纳米结构，其中 α,β-二脱氢-α-氨基酸已成功整合到肽水凝胶剂的结构中，并根据其在潜在生物医学应用中的特性对其进行了讨论。在适当的情况下，将它们的性质与由典型氨基酸组成的相应肽水凝胶剂的性质进行了比较。更广泛地说，我们考虑了天然化合物和药用重要化合物中脱氢氨基酸的存在及其局限性，并考虑了获得脱氢肽的一些合成策略。最后，我们考虑了该研究领域的未来方向。
