Design and synthesis of bile acid–peptide conjugates linked via triazole moiety

Abstract

A conjugation of bile acids with peptides via Cu(I)-catalyzed click chemistry has been described. Novel bile acid-peptide conjugates linked via a 1,2,3-triazole moiety based on cholic, deoxycholic and lithocholic acid derivatives were synthesized using Cu(I)-catalyzed 1,3-dipolar cycloaddition ("click" reaction). It was shown that up to three peptide fragments can be attached to a central steroid core, thus forming complex three-dimensional polyconjugate structures, which can find important applications in biochemistry, medicinal chemistry, and coordination chemistry.

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

“…The corresponding protected azidopeptides 5 [14–15] are accessible by the Ugi multicomponent reaction [16–19] of chiral isocyanoazides 4 [20] with carbonyl compounds, amines and Boc-protected amino acids (Scheme 2). As we showed before, the racemization of the chiral centre of the isocyanoazide does not occur under the conditions of the Ugi reaction [20].…”

“…General procedure for the Ugi-4CC synthesis of peptides 5: As described in [14], the corresponding amine (1 mmol) and acetone or CH 2 O (40% in H 2 O, 1 mmol) were dissolved in 5 mL of MeOH and N -Boc-protected amino acid (1 mmol) and isocyanide 4 (1 mmol) were added at room temperature. The mixture was stirred for 24 h. The solvent was removed in vacuo and the residue was purified by column chromatography (hexanes/ethyl acetate) to give compounds 5 .…”

CuAAC Synthesis and Anion Binding Properties of Bile Acid Derived Tripodal Ligands

“…There are many examples of such conjugates of bile acids with various fragments, which include crown ethers, [13] polyaromatics, [14] and peptides. [15] So, incorporation of bile-acid fragments into an anion receptor can provide a rigid framework for H-bond donors in a binding site and the possibility for further derivatization. The lipophilic nature of bile acids also makes such a receptor compatible with non-polar environments, such as steroid-based amide receptors that are an important class of anion receptors capable of selectively transporting anions through lipid membranes.…”

Chiral Heteroditopic Baskets Designed from Triazolated Calixarenes and Short Peptides

“…The approach used for constructing the CuAAC‐ready azido‐peptide molecules utilizes the efficient Ugi reactions involving chiral isocyanoazides as the key components (Scheme ). N ‐Protected azido‐peptides available in these reactions were shown to extend functionalities of several mono‐– and multi‐propargylated, biorelevant molecules through CuAAC reactions. Along with synthetic particularities of calixarene/peptide CuAAC conjugation, we also studied the ability of the ligands to act as multitopic hosts for metal cations.…”