943296-93-3

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 4467-54-3 l-histidine methyl ester dihydrochloride 
• 1604-44-0 N-α-trifluoroacetyl-L-histidine methyl ester 
• 1401063-48-6 C₁₂H₁₃N₃O₂ 
• 1401003-57-3 C₁₅H₁₄F₃N₃O₃ 
• 98-80-6 phenylboronic acid 
• 1604-44-0 N-α-trifluoroacetyl-L-histidine methyl ester 

Downstream Products

• 1537176-84-3 Boc-Arg-His(phenyl)-Arg-NHBzl 
• 1415241-42-7 Boc-Arg-His(phenyl)-Arg-OMe 
• 1537176-93-4 Arg-His(phenyl)-Arg-NHBzl 
• 1537176-99-0 Arg-His(phenyl)-Arg-OMe 
• 1613201-39-0 His(phenyl)-Arg-NHBzl 
• 1613201-46-9 His(phenyl)-Arg-OMe 
• 1537176-74-1 Boc-His(phenyl)-Arg-NHBzl 
• 1415241-38-1 Boc-His(phenyl)-Arg-OMe 
• 1613201-52-7 N-α-Boc-L-His(phenyl)-NHBzl 
• 1613201-70-9 Trp-His(phenyl)-NHBzl 
• 1613201-58-3 His(phenyl)-NHBzl 
• 1613201-64-1 Boc-Trp-His(phenyl)-NHBzl 

Relevant academic research and scientific papers

Regiospecific direct C-h arylation at the 2-position of l -histidine using arylboronic acids

The first regiospecific direct C-2 arylation procedure for histidine using arylboronic acids has been developed. The reaction allows a one-step synthesis of a large variety of 2-aryl-l-histidines using ammonium persulfate and catalytic silver nitrate in TFA and CHlH (1:1) at ambient temperature.

Modified histidine containing amphipathic ultrashort antifungal peptide, His[2-p-(n-butyl)phenyl]-Trp-Arg-OMe exhibits potent anticryptococcal activity

In pursuit of ultrashort peptide-based antifungals, a new structural class, His(2-aryl)-Trp-Arg is reported. Structural changes were investigated on His-Trp-Arg scaffold to demonstrate the impact of charge and lipophilic character on the biological activity. The presence and size of the aryl moiety on imidazole of histidine modulated overall amphiphilic character, and biological activity. Peptides exhibited IC50 of 0.37–9.66 μg/mL against C. neoformans. Peptide 14f [His(2-p-(n-butyl)phenyl)-Trp-Arg-OMe] exhibited two-fold potency (IC50 = 0.37 μg/mL, MIC = 0.63 μg/mL) related to amphotericin B, without any cytotoxic effects up to 10 μg/mL. Peptide 14f act by nuclear fragmentation, membranes permeabilization, disruption and pore formations in the microbial cells as determined by the mechanistic studies employing Trp-quenching, CLSM, SEM, and HR-TEM. The amalgamation of short sequence, presence of appropriate aryl group on L-histidine, potent anticryptococcal activity, no cytotoxicity, and detailed mechanistic studies directed to the identification of 14f as a new antifungal structural lead.

Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort Amphiphilic Peptide That Exhibits Potent Inhibition of Cryptococcus neoformans

The new structural classes of ultrashort peptides that exhibit potent microbicidal action have potential as future drugs. Herein, we report that C-2 arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent antifungal activity against Cryptococcus neoformans with high selectivity. The most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in vitro activity against C. neoformans (IC50 = 0.35 μg/mL, MIC = MFC = 0.63 μg/mL) with a selectivity index of >28 and 2 times higher potency compared to amphotericin B. Peptide 12f exhibited proteolytic stability, with no apparent hemolytic activity. The mechanism of action study of 12f by confocal laser scanning microscopy and electron microscopy indicates nuclear fragmentation and membrane disruption of C. neoformans cells. Combinations of 12f with fluconazole and amphotericin B at subinhibitory concentration were synergistic against C. neoformans. This study suggests that 12f is a new structural class of amphiphilic peptide with rapid fungicidal activity caused by C. neoformans.

Synthesis and antimicrobial activities of His(2-aryl)-Arg and Trp-His(2-aryl) classes of dipeptidomimetics

In this communication, we report the design, synthesis and in vitro antimicrobial activity of ultra short peptidomimetics. Besides producing promising antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), the dipeptidomimetics exhibited high antifungal activity against C. neoformans with IC50 values in the range of 0.16-19 μg mL-1. The most potent analogs exhibited 4-fold higher activity than the currently used drug amphotericin B, with no apparent cytotoxicity in a panel of mammalian cell lines. This journal is the Partner Organisations 2014.

Discovery of short peptides exhibiting high potency against Cryptococcus neoformans

Rapid increase in the emergence of resistance against existing antifungal drugs created a need to discover new structural classes of antifungal agents. In this study we describe the synthesis of a new structural class of short antifungal peptidomimetcis, their activity, and plausible mechanism of action. The results of the study show that peptides 11e and 11f are more potent than the control drug amphotericin B, with no cytotoxicity to human cancer cells and noncancerous mammalian kidney cells. The selectivity of peptides to fungus is depicted by transmission electron microscopy studies, and it revealed that 11e possibly disrupts the model membrane of the fungal pathogen.