189249-10-3

Usage

Uses

Used in Organic Synthesis:
Fomc-cis-L-hydroxyproline-OH is used as a building block in peptide synthesis for creating peptides with specific structural and functional properties. Its unique cis configuration allows for the formation of distinct peptide structures, which can be beneficial in various applications.
Used in Biochemical Research:
In biochemical research, Fomc-cis-L-hydroxyproline-OH serves as a valuable tool for studying the properties and functions of peptides and proteins. Its unique structure enables researchers to investigate the effects of cis isomerism on protein folding, stability, and interactions with other biomolecules.
Used in Pharmaceutical Development:
Fomc-cis-L-hydroxyproline-OH is utilized as a chiral auxiliary in asymmetric synthesis, which is crucial for the development of enantiomerically pure drugs. Its ability to induce chirality in the synthesis process can lead to the production of more effective and selective pharmaceutical agents.
Used in Drug Development:
Fomc-cis-L-hydroxyproline-OH is also used as a component in the development of new drugs and therapies. Its unique structural properties can contribute to the design of novel drug candidates with improved pharmacological properties, such as enhanced potency, selectivity, and reduced side effects.

Upstream product

• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 618-27-9 hydroxy L-proline 
• 147-85-3 L-proline 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 

Downstream Products

• 268729-12-0 N-(9-fluorenylmethoxycarbonyl)-(2S,4S)-4-tert-butoxyproline 
• 1190083-09-0 C₄₆H₇₁N₁₁O₁₂S₂ 
• 847978-87-4 [1-benzyl-2-(4-tert-butoxy-2-methylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid 9H-fluoren-9-ylmethyl ester 

Relevant academic research and scientific papers

Evidence for a stereoelectronic effect in human oxygen sensing

How PHDs achieve specificity: trans-4-prolyl hydroxylation of the transcription factor HIF occurs with stereochemical retention. Substrate-analogue studies show how the von Hippel Lindau tumor suppressor protein (pVHL) and the oxygen-sensing hydroxylases (PHDs) achieve specificity for hydroxy prolyl/prolyl residues for the C4-exo/endo prolyl conformations, respectively.

Discovery of New Fe(II)/α-Ketoglutarate-Dependent Dioxygenases for Oxidation of l-Proline

Genome mining for novel Fe(II)/α-ketoglutarate-dependent dioxygenases (αKGDs) to expand the enzymatic repertoire in the oxidation of l-proline is reported. Through clustering of proteins, we predicted regio- and stereoselectivity in the hydroxylation reaction and validated this hypothesis experimentally. Two novel byproducts in the reactions with enzymes from Bacillus cereus and Streptomyces sp. were isolated, and the structures were determined to be a 3,4-epoxide and a 3,4-diol, respectively. The mechanism for the formation of the epoxide was investigated by performing an 18O-labeling experiment. We propose that the mechanism proceeds via initial cis-3-hydroxylation followed by ring closure. A biocatalytic step was run on subgram quantities of starting material without any significant optimization of the conditions. However, the substrate concentration was 40-fold higher than the usual reported titers for recombinant P450-mediated hydroxylations, showing the synthetic potential of αKGDs on a preparative scale.

Total Synthesis of the Death Cap Toxin Phalloidin: Atropoisomer Selectivity Explained by Molecular-Dynamics Simulations

Phallotoxins and amatoxins are a group of prominent peptide toxins produced by the death cap mushroom Amanita phalloides. Phalloidin is a bicyclic cyclopeptide with an unusual tryptathionin thioether bridge. It is a potent stabilizer of filamentous actin and in a fluorescently labeled form widely used as a probe for actin binding. Herein, we report the enantioselective synthesis of the key amino acid (2S,4R)-4,5-dihydroxy-leucine as a basis for the first total synthesis of phalloidin, which was accomplished by two different synthesis strategies. Molecular-dynamics simulations provided insights into the conformational flexibility of peptide intermediates of different reaction strategies and showed that this flexibility is critical for the formation of atropoisomers. By simulating the intermediates, rather than the final product, molecular-dynamics simulations will become a decisive tool in orchestrating the sequence of ring formation reactions of complex cyclic peptides.

Conformational changes associated with post-translational modifications of pro143 in Skp1 of dictyostelium -a dipeptide model system

Prolyl hydroxylation and subsequent glycosylation of the E3SCF ubiquitin ligase subunit Skp1 affects its conformation and its interaction with F-box proteins and, ultimately, O2-sensing in the organism. Taking a reductionist approach to understand the molecular basis for these effects, a series of end-capped Thr-Pro dipeptides was synthesized, tracking the sequential post-translational modifications that occur in the protein. The conformation of the pyrrolidine ring in each compound was gauged via coupling constants (3JHα,Hβ) and the electronegativity of the Cγ-substituents by chemical shifts (13C). The equilibrium between the cis-trans conformations about the central prolyl peptide bond was investigated by integration of signals corresponding to the two species in the 1H NMR spectra over a range of temperatures. These studies revealed an increasing preference for the trans-conformation in the order Pro a reduced rate for the trans-to-cis conversion and a significant increase in the cis-to-trans conversion upon hydroxylation of the proline residue in the dipeptide. NOE experiments suggest that the Thr side chain pushes the sugar away from the pyrrolidine ring. These effects, which depended on the presence of the N-terminal Thr residue, offer a mechanism to explain altered properties of the corresponding full-length proteins.

The impact of pyrrolidine hydroxylation on the conformation of proline-containing peptides

(Chemical Equation Presented) A series of eight dipeptides of the general formula Ac-Phe-Pro*-NHMe was synthesized and the thermodynamics of the cis → trans isomerization about the central amide bond were studied by NMR. Pro* represents the following prol