116857-07-9Relevant academic research and scientific papers
An alternative solid-phase approach to C1-oxytocin
Mayer, John P.,Heil, James R.,Zhang, Jingwen,Munson, Mark C.
, p. 7387 - 7390 (1995)
A general, solid-phase method based on in situ formation of a cystathionine residue is described. The procedure allows for the introduction of a thioether moiety in place of a native disulfide bond and is illustrated here by the synthesis of C1-oxytocin 1.
Total Chemical Synthesis of an Intra-A-Chain Cystathionine Human Insulin Analogue with Enhanced Thermal Stability
Karas, John A.,Patil, Nitin A.,Tailhades, Julien,Sani, Marc-Antoine,Scanlon, Denis B.,Forbes, Briony E.,Gardiner, James,Separovic, Frances,Wade, John D.,Hossain, Mohammed Akhter
, p. 14743 - 14747 (2016)
Despite recent advances in the treatment of diabetes mellitus, storage of insulin formulations at 4 °C is still necessary to minimize chemical degradation. This is problematic in tropical regions where reliable refrigeration is not ubiquitous. Some degradation byproducts are caused by disulfide shuffling of cystine that leads to covalently bonded oligomers. Consequently we examined the utility of the non-reducible cystine isostere, cystathionine, within the A-chain. Reported herein is an efficient method for forming this mimic using simple monomeric building blocks. The intra-A-chain cystathionine insulin analogue was obtained in good overall yield, chemically characterized and demonstrated to possess native binding affinity for the insulin receptor isoform B. It was also shown to possess significantly enhanced thermal stability indicating potential application to next-generation insulin analogues.
Regio- and Stereoselective Chan-Lam-Evans Enol Esterification of Carboxylic Acids with Alkenylboroxines
Steemers, Luuk,Wijsman, Linda,van Maarseveen, Jan H.
supporting information, p. 4241 - 4245 (2018/10/02)
Efficient and scalable Cu(II)-mediated enol esterification methodology of carboxylic acids from alkenyl boroxines and boronic acids is presented. The reaction shows a wide scope in aliphatic and aromatic carboxylic acids in combination with several alkenyl boroxines. In the case of 2-substituted alkenyl boroxines the double bond configuration was fully retained in the enol ester product. Also N-hydroxyimides and imides could be transformed in the respective amidooxy vinyl enol ethers and vinyl enamides. Finally, with the exception of methionine, all other 19 canonical amino acids showed their compatibility to give the enol esters in a stereoselective fashion. (Figure presented.).
A microwave-assisted synthesis of (S)-N-protected homoserine γ-lactones from l-aspartic acid
Singh, Suneel P.,Michaelides, Alex,Merrill, A. Rod,Schwan, Adrian L.
, p. 6825 - 6831 (2011/10/08)
A three-pot preparation of (S)-N-protected homoserine γ-lactones is presented. Conversion of N-protected l-aspartic acid to an oxazolidinone is followed by selective reduction/acid-catalyzed cyclization to deliver the lactones. Microwave irradiation proved valuable for improving the latter reaction steps in some cases.
Opioid peptides: synthesis and biological properties of [(N gamma-glucosyl,N gamma-methoxy)-alpha, gamma-diamino-(S)-butanoyl]4-deltorphin-1-neoglycopeptide and related analogues.
Filira, Fernando,Biondi, Barbara,Biondi, Laura,Giannini, Elisa,Gobbo, Marina,Negri, Lucia,Rocchi, Raniero
, p. 3059 - 3063 (2007/10/03)
The [D-Ala2]deltorphin 1 sequence in which the aspartic acid residue is replaced by the N gamma-OCH3-alpha, gamma-diamino (S) butanoyl residue was synthesized using the Fmoc-chemistry-based solid phase procedure. The resulting deltorphin analogue was chemoselectively glucosylated by reaction with unprotected D-glucose (Glc). The Asn4-, (2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-galactopyranosyl)-Asn4- and the (2-acetamido-2-deoxy-D-galactopyranosyl)-Asn4-deltorphin I were also prepared for comparison. The affinity of the new compounds for the delta-opioid receptor was expressed by the inhibition constant (Ki) of the binding of the delta-receptor selective ligand [3H]naltrindole (NTI) to rat brain membrane preparations. The in vitro biological activity of the synthetic peptides was compared with that of the mu-opioid receptor agonist dermorphin in guinea pig ileum (GPI) preparations and with that of the delta-opioid receptor agonist deltorphin I in mouse vas deferens (MVD) preparations. The substitution of Asp4 with Asn failed to affect drastically the Ki and IC50 values for delta-sites, suggesting that an electrostatic interaction does not play an essential role in the binding to delta-opioid sites. The steric hindrance of the side chain of the residue in position 4 affects binding to delta-sites. The increase of the Ki value is smaller when the sugar-peptide linkage involves the gamma-nitrogen of the Dab residue in comparison with the Asn amide side chain.
Nucleophilic substitution of protected 2-amino-4-butanoic acid. An easy route to exotic amino acids and conformationally constrained peptides
Ciapetti, Paola,Mann, Andre,Shoenfelder, Angele,Taddei, Maurizio
, p. 3843 - 3846 (2007/10/03)
The synthesis of a series of novel α-amino acids based on the nucleophilic substitution of protected 2-amino-4-bromobutanoic acid (1) is described. Basic, acidic or neutral amino acids can be obtained; chimerical amino acids carrying a coenzyme type structure in the side chain, multifunctional amino acids for the synthesis of cross-linked peptides or dendrimers and conformationally constrained peptides can also be obtained.
