647847-95-8

Upstream product

• 672-15-1 L-homoserine 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 
• 100-39-0 benzyl bromide 
• 71989-14-5 Fmoc-(tBu)Asp-OH 
• 172525-85-8 N^α-(Fluoren-9-ylmethoxycarbonyl)-L-homoserine 
• 86060-83-5 N-(9-fluorenylmethoxycarbonyl)-L-aspartyl α-benzyl ester 
• 117854-05-4 N-(9-fluorenylmethoxycarbonyl)-L-aspartyl β-tert-butyl α-benzyl diester 

Downstream Products

• 511546-75-1 benzyl 2-fluorenylmethyloxycarbonyl-3-formylpropanoate 
• 546108-81-0 vinyl-glycine 
• 647847-98-1 benzyl N^α-fluorenylmethyloxycarbonyl-N^γ-(methoxy)imino-α-amino-L-butanoate 
• 647848-00-8 benzyl N^α-fluorenylmethyloxycarbonyl-N^γ-methoxy-α,γ-diamino-L-butanoate 
• 647848-02-0 benzyl N^α-fluorenylmethyloxycarbonyl-N^γ-tert-butyloxycarbonyl-N^γ-methoxy-α,γ-diamino-L-butanoate 
• 1160862-44-1 (2S,4S)-benzyl 2-oxo-3-(9-fluorenylmethoxycarbonyl)-1,2,3-oxathiazinane-4-carboxylate 
• 1160862-18-9 (2R,4S)-benzyl 2-oxo-3-(9-fluorenylmethoxycarbonyl)-1,2,3-oxathiazinane-4-carboxylate 
• 1415986-37-6 C₅₂H₅₀N₃O₁₃P 
• 1415986-38-7 C₅₄H₆₁N₄O₁₆P 
• 1415986-39-8 C₄₉H₅₃N₄O₁₄P*ClH 
• 1415986-42-3 C₆₃H₇₀N₅O₁₇P 
• 1415986-36-5 C₃₃H₃₁N₂O₉P 

Relevant academic research and scientific papers

Synthesis of constrained tetracyclic peptides by consecutive CEPS, CLIPS, and oxime ligation

In Nature, multicyclic peptides constitute a versatile molecule class with various biological functions. For their pharmaceutical exploitation, chemical methodologies that enable selective consecutive macrocyclizations are required. We disclose a combination of enzymatic macrocyclization, CLIPS alkylation, and oxime ligation to prepare tetracyclic peptides. Five new small molecular scaffolds and differently sized model peptides featuring noncanonical amino acids were synthesized. Enzymatic macrocyclization, followed by one-pot scaffold-assisted cyclizations, yielded 21 tetracyclic peptides in a facile and robust manner.

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.

CHELATED PSMA INHIBITORS

Compounds as defined herein are provided which are useful in (1) diagnostic methods for detecting and/or identifying cells presenting PSMA; (2) compositions comprising a compound of the invention together with a pharmaceutically acceptable diluent; and (3) methods for imaging prostate cancer cells.

PROCESSES FOR PREPARING AMINO-SUBSTITUTED GAMMA-LACTAMS

The present application describes general process for the preparation of amino-substitued gamma-lactams involving the reaction of synthons of the general Formulae (I) and (VI): with amines. The processes are amenable to solid phase synthetic techniques and therefore allow the efficient incorporation of amino-substitued gamma-lactams into a wide variety of structural scaffolds, including, in particular peptides.

Positional scanning for peptide secondary structure by systematic solid-phase synthesis of amino lactam peptides

Incorporation of amino lactams into biologically active peptides has been commonly used to restrict conformational mobility, enhance selectivity, and increase potency. A solid-phase method using a Fmoc-protection strategy has been developed for the systematic synthesis of peptides containing configurationally defined α- and β-amino γ-lactams. N-Alkylation of N-silyl peptides with five- and six-member cyclic sulfamidates 9 and 8 minimized bis-alkylation and provided N-alkyl peptides,which underwent lactam annulation under microwave heating. Employing th is solid-phase protocol on the growth hormone secretagogue GHRP-6, as well as on the allosteric modulator of the IL-1 receptor 101.10, has furnished 16 lactam derivatives and validated the effectiveness of this approach on peptides bearing aliphatic, aromatic, branched, charged, and heteroatomic side chains. The binding affinity IC 50 values of the GHRP-6 lactam analogues on both the GHS-R1a and CD36 receptors are reported as well as inhibition of thymocyte proliferation measurements for the 101.10 lactam analogues. In these cases, lactam analogues were prepared exhibiting similar or improved properties compared with the parent peptide. Considering the potential for amino lactams to induce peptide turn conformations, the effective method described herein for their supported construction on growing peptides, and for the systematical amino lactam scan of peptides, has proven useful for the rapid identification of the secondary structure necessary for peptide biological activity.

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.

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.