Kammeyer Jacquelin K, Blum Angela P, Adamiak Lisa, Hahn Michael E, Gianneschi Nathan C
Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
Polym Chem. 2013;41:3929-3933. doi: 10.1039/C3PY00526G.
A study was conducted to survey the tolerance of ring-opening metathesis polymerization (ROMP) with respect to amino acid (a.a) identity of pentapeptide-modified norbornene-based monomers. A library of norbornyl-pentapeptides were prepared with the general structure, norbornyl-GXPLX, where residue 'X' was changed at each of the two positions (2 or 5) alternately to consist of the natural amino acids F, A, V, R, S, K, N, T, M, Q, H, W, C, Y, E, Q, and D. Each peptide monomer, free of protecting groups, was mixed in turn under a standard set of polymerization conditions with the ROMP initiator (IMesH)CHN)(Cl)Ru=CHPh. Two sets of polymerization reactions were performed, one with Monomer:Initiator (M:I) ratio of 20:1, and another with M:I of 200:1. For the nucleophilic amino acids cysteine and lysine, polymerization reactions were quantitatively compared to those of their protected analogues. Furthermore, we describe polymerization of macromonomers containing up to 30 a.a. to test for tolerance of ROMP to peptide molecular weight. These reactions were studied via SEC-MALS and NMR. Finally, with knowledge of sequence scope in hand, we prepared a set of enzyme-substrate containing brush polymers and studied them with respect to their bioactivity.
开展了一项研究，以调查开环易位聚合（ROMP）对五肽修饰的降冰片烯基单体氨基酸（a.a）同一性的耐受性。制备了一组降冰片基五肽，其具有通式结构降冰片基-GXPLX，其中残基“X”在两个位置（2或5）之一交替变化，由天然氨基酸F、A、V、R、S、K、N、T、M、Q、H、W、C、Y、E、Q和D组成。每种无保护基团的肽单体依次在一组标准聚合条件下与ROMP引发剂(IMesH)CHN)(Cl)Ru=CHPh混合。进行了两组聚合反应，一组单体与引发剂（M:I）比例为20:1，另一组M:I比例为200:1。对于亲核氨基酸半胱氨酸和赖氨酸，将聚合反应与其受保护类似物的反应进行了定量比较。此外，我们描述了含有多达30个a.a.的大分子单体的聚合反应，以测试ROMP对肽分子量的耐受性。通过尺寸排阻色谱-多角度激光光散射（SEC-MALS）和核磁共振（NMR）研究了这些反应。最后，掌握了序列范围后，我们制备了一组含酶底物的刷状聚合物，并对其生物活性进行了研究。
