Synthesis of norbornenyl polymers with bioactive oligopeptides by ring-opening metathesis polymerization
Synthesis of norbornenyl polymers with bioactive oligopeptides by ring-opening metathesis polymerization
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DOI：
10.1021/ma000460c
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发表时间：
2000-08-22
期刊：
影响因子：
5.5
通讯作者：
Grubbs, RH
中科院分区：
文献类型：
--
作者：
Maynard, HD;Okada, SY;Grubbs, RH
以钌为引发剂，通过开环易位聚合（ROMP）合成了含有甘氨酸-精氨酸-甘氨酸-天冬氨酸（GRGD）和丝氨酸-精氨酸-天冬酰胺（SRN）细胞粘附侧链的双烯基聚合物。最初，使用Ru=CHPh（Cl）（2）（PCy 3）（2）（1）作为引发剂，合成了具有直接或通过乙基和丙基间隔基连接到各种C1-C6烯基主链的侧基甘氨酸、丙氨酸或五（乙二醇）（EO 5）单元的更简单的聚合物。比较了这些聚合物的分子量、PDI、聚合时间、产率和玻璃化转变温度。作为该比较的结果，选择聚（5-异戊烯-2-羧基）作为含有聚合物的更复杂的寡肽的主链，并且制备具有侧基EO 5（21）、GRGD（24）和SRN（25）单元的异戊烯单体。使用1作为引发剂，使单体21和24共聚以形成含有9.2mol%GRGD（26 a）的聚（异戊二烯）。然而，掺入更大量的GRGD导致呈现双峰分子量分布的聚合物的产率极低。使用新开发的、活性更高的2，3-二氢咪唑亚基引发剂Ru=CHPh（Cl）（2）（PCy 3）（DHIMes）（2）和Ru =CH-CH=C（CH 3）（2）（Cl）（2）（PCp 3）（DHIMes）（3），以良好的产率（32-92%）合成了具有较大量GRGD和SRN的均聚物和共聚物，具有单峰分子量分布。以这种方式，合成了具有49摩尔% GRGD（26 b）、53摩尔% SRN（27 b）或32摩尔% GRGD和21摩尔% SRN（28 a）的含EO 5的共聚物，以及具有53摩尔% GRGD和47摩尔% SRN的共聚物28 b。为了改变GRGD的呈现，还合成了在GRGD和主链（30）之间具有丙基间隔基的含EO 5的共聚物。
Synthetic norbornenyl polymers with pendent cell adhesive sequences glycine-arginine-glycine-aspartic acid (GRGD) and serine-arginine-asparagine (SRN) were synthesized by ring-opening metathesis polymerization (ROMP) using newly developed ruthenium initiators. Initially, simpler polymers with pendent glycine, alanine, or penta(ethylene glycol) (EO5) units attached directly or through ethyl and propyl spacers to various norbornenyl backbones were synthesized using Ru=CHPh(Cl)(2)(PCy3)(2) (1) as the initiator. The molecular weights, PDI's, polymerization times, yields, and glass transition temperatures were compared for these polymers. As a result of this comparison, poly(5-norbornene-2-carboxyl) was chosen as the backbone for the more complex oligopeptide containing polymers, and norbornene monomers with pendent EO5 (21), GRGD (24), and SRN (25) units were made. Monomers 21 and 24 were copolymerized to form a poly(norbornene) containing 9.2 mol % GRGD (26a) using 1 as the initiator. However, incorporating larger amounts of GRGD resulted in extremely low yields of polymers that exhibited bimodal molecular weight distributions. Homopolymers and copolymers with larger amounts of GRGD and SRN were synthesized in good yields (32-92%) with monomodal molecular weight distributions using the newly developed, more active, 2,3-dihydroimidazolylidene initiators, Ru=CHPh(Cl)(2)(PCy3)(DHIMes) (2) and Ru=CH-CH=C(CH3)(2)(Cl)(2)(PCp3)(DHIMes) (3). In this way, EO5 containing copolymers with 49 mol % GRGD (26b), 53 mol % SRN (27b), or 32 mol % GRGD and 21 mol % SRN (28a) were synthesized, as well as copolymer 28b with 53 mol % GRGD and 47 mol % SRN. To alter the presentation of the GRGD, an EO5 containing copolymer with a propyl spacer between the GRGD and the backbone (30) was also synthesized.