Synthesis and characterization of polymer-(multi)-peptide conjugates for control of specific cell aggregation
Synthesis and characterization of polymer-(multi)-peptide conjugates for control of specific cell aggregation
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DOI：
10.1163/156856298x00613
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发表时间：
1998-01-01
影响因子：
3.6
通讯作者：
Saltzman, WM
中科院分区：
文献类型：
--
作者：
Belcheva, N;Baldwin, SP;Saltzman, WM
一种新的合成方法已被应用于获得新型的含二、四和(多)-肽的聚合物共轭化合物，其定量产率和高共轭程度。以甘氨酸-甘氨酸-酪氨酸-精氨酸为模型肽和甘氨酸-精氨酸-甘氨酸-天冬氨酸-天冬氨酸-酪氨酸-酪氨酸为模型肽，在有机介质中通过缩合反应合成了聚乙二醇双(N-羟基琥珀酰亚胺基)聚乙二醇酯(M-w=200、600、1400、2000和3400)。研究了聚丙烯酸及其共聚物(M-w=2000和5000)与L-色氨酸和GGYR反应的多官能团线型聚合物。以StarBurst(R)树枝状大分子PAMAM(G=3)、‘短’和‘长’链聚乙二醇活性酯和GRGDY为原料，成功地合成了选择性聚合物-(多)肽连接物。中间体前体物和多肽结合物的结构通过光谱分析(UV-Vis、FTIR、H-1-核磁共振)和色谱分析(RP-KPLC和SEC)确证。通过改变互连聚合物的性质--如疏水性、相对分子质量和官能度--合成了一组聚合物-GRGDY偶联物。
A new synthetic approach has been applied to obtain novel di-, tetra-, and (multi)-peptide containing polymer conjugates in quantitative yields with a high degree of conjugation. Bis-(N-hydroxysuccinimidyl) esters of PEG (M-w = 200, 600, 1400, 2000, and 3400) were synthesized and studied in a condensation reaction with synthetic peptides: glycine-glycine-tyrosine-arginine (GGYR), a model peptide, and glycine-arginine-glycine-aspartic acid-tyrosine (GRGDY), a sequence known to promote cell adhesion and aggregation Tetra-substituted derivatives of PEG-based conjugates were synthesized by coupling L-aspartic acid and L-aspartyl-L-phenylalanine through a condensation procedure in organic media. Poly(acrylic acid) and co-polymers (M-w = 2000 and 5000) were studied as a model of multifunctional linear polymers in the reaction with L-tryptophan and GGYR. Alternative polymer-(multi)peptide conjugates were successfully synthesized using Starburst(R) dendrimer PAMAM (G = 3), 'short' and 'long'-chain PEG-based active esters and GRGDY. The structure of the intermediate precursors and peptide-conjugates was confirmed by spectral (UV-Vis, FTIR, H-1-NMR) and chromatographic (RP-KPLC and SEC) methods. By varying the properties of the interconnecting polymer -- such as hydrophobicity, molecular weight, and functionality -- a set of polymer-GRGDY conjugates was synthesized.