Sonogashira, CuAAC, and Oxime Ligations for the Synthesis of MnI Tricarbonyl PhotoCORM Peptide Conjugates
Sonogashira, CuAAC, and Oxime Ligations for the Synthesis of MnI Tricarbonyl PhotoCORM Peptide Conjugates
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DOI：
10.1002/ejic.201402123
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发表时间：
2014-06
影响因子：
2.3
通讯作者：
S. Pai;K. Radacki;U. Schatzschneider
中科院分区：
文献类型：
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作者：
S. Pai;K. Radacki;U. Schatzschneider
在这项工作中，面三羰基锰（I）配合物[Mn（bpeaCH 2C 6 H4 R）（CO）3] PF 6纳入功能化的2，2-双（吡唑基）乙胺（bpea）配体与R = I，C = CH，CHO已被探索其效用在生物正交耦合载体肽轴承N-末端炔，叠氮化物，和氨氧基残基。作为模型系统，使用转化生长因子β识别（TGF-β）肽序列R′-Leu-Pro-Leu-Gly-Asn-Ser-His-OH，其中R′是与金属络合物官能团互补的反应性基团。使用无催化剂的肟连接得到最稳定的缀合物，即使在重复冻融循环后，通过HPLC在96小时内也没有观察到降解。通过使用肌红蛋白测定，研究了母体复合物以及官能化的肽用于光活化的CO向血红素蛋白的递送，并且发现具有基本上相同的释放性质。本工作建立了一种新的策略，共轭光活化CO释放分子（PhotoCORM）的生物载体系统。
In this work, facial tricarbonylmanganese(I) complexes [Mn(bpeaCH2C6H4R)(CO)3]PF6 incorporating a functionalized 2,2-bis(pyrazolyl)ethylamine (bpea) ligand with R = I, C≡CH, and CHO have been explored for their utility in bioorthogonal coupling to carrier peptides bearing N-terminal alkyne, azide, and aminoxy residues. As a model system, the transforming growth factor β-recognizing (TGF-β) peptide sequence R′-Leu-Pro-Leu-Gly-Asn-Ser-His-OH was used in which R′ is the reactive group complementary to the metal complex functionality. The use of catalyst-free oxime ligation gave the most stable conjugate with no degradation observed by HPLC over 96 h even after repeated freeze–thaw cycles. Both the parent complex as well as the functionalized peptide were investigated for photoactivated CO delivery to heme proteins by using the myoglobin assay and found to have essentially identical release properties. This work has established a new strategy for the conjugation of photoactivatable CO-releasing molecules (PhotoCORMs) to biological carrier systems.