635757-72-1

Upstream product

• 36016-38-3 tert-Butyl N-hydroxycarbamate 
• 106-96-7 propargyl bromide 

Relevant academic research and scientific papers

MULTICYCLIC PEPTIDES AND METHODS FOR THEIR PREPARATION

The invention relates to methods for preparing a compound comprising a peptide attached to a molecular scaffold whereby multiple peptide loops are formed, to compounds that can be obtained with such methods and uses thereof.

SELECTIVE KILLING OF TUMORS OF THE HEMATOPOIETIC AND LYMPHOID TISSUES

R1, R2, R3, R4, R5 are each independently hydrogen (H), C1-6 alkyl, F, Cl, or Br; and n is 1 to 5.

METHODS AND COMPOSITIONS FOR SITE-SPECIFIC LABELING OF PEPTIDES AND PROTEINS

Methods and compositions are provided for covalently linking a chemical species to a recombinant or synthetic polypeptide. The methods involve the reaction of a thioester-comprising polypeptide with a reagent comprising a reactive amino-thiol group connec

Macrocyclization of Organo-Peptide Hybrids through a Dual Bio-orthogonal Ligation: Insights from Structure-Reactivity Studies

Macrocycles constitute an attractive structural class of molecules for targeting biomolecular interfaces with high affinity and specificity. Here, we report systematic studies aimed at exploring the scope and mechanism of a novel chemo-biosynthetic strategy for generating macrocyclic organo-peptide hybrids (MOrPHs) through a dual oxime-/intein-mediated ligation reaction between a recombinant precursor protein and bifunctional, oxyamino/1,3-amino-thiol compounds. An efficient synthetic route was developed to access structurally different synthetic precursors incorporating a 2-amino- mercaptomethyl-aryl (AMA) moiety previously found to be important for macrocyclization. With these compounds, the impact of the synthetic precursor scaffold and of designed mutations within the genetically encoded precursor peptide sequence on macrocyclization efficiency was investigated. Importantly, the desired MOrPHs were obtained as the only product from all the different synthetic precursors probed in this study and across peptide sequences comprising four to 15 amino acids. Systematic mutagenesis of the "i-1" site at the junction between the target peptide sequence and the intein moiety revealed that the majority of the 20 amino acids are compatible with MOrPH formation; this enables the identification of the most and the least favorable residues for this critical position. Furthermore, interesting trends with respect to the positional effect of conformationally constrained (Pro) and flexible (Gly) residues on the reactivity of randomized hexamer peptide sequences were observed. Finally, mechanistic investigations enabled the relative contributions of the two distinct pathways (side-chain→C-end ligation versus C-end→side-chain ligation) to the macrocyclization process to be dissected. Altogether, these studies demonstrate the versatility and robustness of the methodology to enable the synthesis and diversification of a new class of organo-peptide macrocycles and provide valuable structure-reactivity insights to inform the construction of macrocycle libraries through this chemo-biosynthetic strategy.