Exploring the copper binding ability of Mets7 hCtr‐1 protein domain and His7 derivative: An insight in Michael addition catalysis

Abstract

Mets7 is a methionine-rich motif present in hCtr-1 transporter that is involved in copper cellular trafficking. Its ability to bind Cu(I) was recently exploited to develop metallopeptide catalysts for Henry condensation. Here, the catalytic activity of Mets7-Cu(I) complex in Michael addition reactions has been evaluated. Furthermore, His7 peptide, in which Met residues have been substituted with His ones, was also prepared. This substitution allowed His7 to coordinate Cu(II), with the obtainment of a stable turn conformation as evicted by CD experiments. His7-Cu(II) proved also to be a better catalyst than Mets7-Cu(I) in the addition reaction. In particular, when the substrate was the (E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1one, a conversion of 71% and a significative 58 % of e.e. was observed.

New sp3 diphosphine-based rhodium catalysts for the asymmetric conjugate addition of aryl boronic acids to 3-azaarylpropenones

“…Conversely, the addition of phenylboronic acid was evaluated for four different 3-azaarylpropenones as substrates, hereafter called 1 ((E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-one), 2 ((E)-1-phenyl-3- and 4 ((E)-3-(1-methyl-1H-imidazol-4-yl)-1-phenylprop-2-en-1-one) respectively. 26 In order to get a prognostic insight into the reactivity of different rhodium based catalytic systems in this type of reaction, we employed diphophine ligands characterized by varied types of chirality: phosphorus based ligands bearing only an atropoisomeric chirality as in (S)-TetraMe-BITIANP (L1) and (S)-BITIANP (L2), 23,27 ; diphosphines endowed with a mixed chirality (both sp 3 and atropoisomeric) as in (S,S,Sax)-DIOPHEP (L3) 28 and (R,Rax)-ISAPHOS C1 (L4) and (S,Rax,Rax)-ISAPHOS C2 (L5) 29,30 ; or only a sp 3 chirality as in the case of (R,R)-ZEDPHOS (L6). 20 Table 1.…”

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

“…The oxidation of organic substrates has also been reported, where SCS interactions have been employed to control protein–substrate interactions. Furthermore, artificial Cu proteins have been repurposed to catalyze a number of unnatural reactions including the D-A reaction, , F-C alkylation, Michael addition, and alkene hydration . In these cases, the SCS has been employed to enforce product selectivity via substrate–SCS interactions.…”

“…This effect was supported by a subsequent mutagenesis study, in which the H52A/C106A or H52A/C106S mutation removes or disorientates the H-bond and reduces the Si selectivity, whereas the H54A/H58A/F104W mutation enhances the steric hindrance from residue 104 to increase the Re selectivity. Another recent study by Rimoldi et al used two simple peptides derived from the methionine-rich motif in hCtr-1 transporter to catalyze the Michael addition reaction . The yield was comparable to those of previous studies with a relatively lower enantioselectivity, possibly due to the absence of the SCS interactions of more complex proteins.…”

A Non‐coded β2,2‐Amino Acid with Isoxazoline Core Able to Stabilize Peptides Folding through an Unprecedented Hydrogen Bond

“…Methyl 5-(Aminomethyl)-3-phenyl-4,5-dihydroisoxazole-5-carboxylate (5). In a round bottom flask equipped with magnetic stirrer, 4 (771 mg, 2.96 mmol) was suspended in THF (29.6 mL) to obtain a 0.1M solution.…”