The third-generation peptide-dendrimer B1 (AcES)8(BEA) 4(K-Amb-Y)2BCD-NH2 (B=branching (S)-2,3-diaminopropanoic acid, K=branching lysine, Amb=4-aminomethyl-benzoic acid) is the first synthetic model for cobalamin-binding proteins and binds cobalamin strongly (Ka=5.0×106M-1) and rapidly (k2= 346m-1 s-1) by coordination of cobalt to the cysteine residue at the dendrimer core. A structure-activity relationship study is reported concerning the role of negative charges in binding. Substituting glutamates (E) for glutamines (Q) in the outer branches of B1 to form N3 (AcQS)8(BQA)4(B-Amb-Y)2BCD- NH2 leads to stronger (Ka=12.0×106M -1) but slower (k2= 67M-1 s-1) cobalamin binding. CD and FTIR spectra show that the dendrimers and their cobalamin complexes exist as random-coil structures without aggregation in solution. The hydrodynamic radii of the dendrimers determined by diffusion NMR either remains constant or slightly decreases upon binding to cobalamin; this indicates the formation of compact, presumably hydrophobically collapsed complexes.
Uhlich, N., Natalello, A., Kadam, R., Doglia, S., Reymond, J., & Darbre, T. (2010). Structure and binding of peptide-dendrimer ligands to vitamin B12. CHEMBIOCHEM, 11(3), 358-365 [10.1002/cbic.200900657].
Citazione: | Uhlich, N., Natalello, A., Kadam, R., Doglia, S., Reymond, J., & Darbre, T. (2010). Structure and binding of peptide-dendrimer ligands to vitamin B12. CHEMBIOCHEM, 11(3), 358-365 [10.1002/cbic.200900657]. | |
Tipo: | Articolo in rivista - Articolo scientifico | |
Carattere della pubblicazione: | Scientifica | |
Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
Titolo: | Structure and binding of peptide-dendrimer ligands to vitamin B12 | |
Autori: | Uhlich, N; Natalello, A; Kadam, R; Doglia, S; Reymond, J; Darbre, T | |
Autori: | ||
Data di pubblicazione: | 2010 | |
Lingua: | English | |
Rivista: | CHEMBIOCHEM | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1002/cbic.200900657 | |
Appare nelle tipologie: | 01 - Articolo su rivista |