- Boosting Fmoc Solid-Phase Peptide Synthesis by Ultrasonication
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We investigated the ultrasonication-mediated effects on the Fmoc-based solid-phase peptide synthesis (SPPS). Our study culminated with the development of an ultrasound-assisted strategy (US-SPPS) that allowed for the synthesis of different biologically active peptides (up to 44-mer), with a remarkable savings of material and reaction time. Noteworthy, ultrasonic irradiation did not exacerbate the main side reactions and improved the synthesis of peptides endowed with "difficult sequences", placing the US-SPPS among the current high-efficient peptide synthetic strategies.
- Merlino, Francesco,Tomassi, Stefano,Yousif, Ali M.,Messere, Anna,Marinelli, Luciana,Grieco, Paolo,Novellino, Ettore,Cosconati, Sandro,Di Maro, Salvatore
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supporting information
p. 6378 - 6382
(2019/09/06)
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- Design of MC1R Selective γ-MSH Analogues with Canonical Amino Acids Leads to Potency and Pigmentation
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Melanoma is a lethal form of skin cancer. Skin pigmentation, which is regulated by the melanocortin 1 receptor (MC1R), is an effective protection against melanoma. However, the endogenous MC1R agonists lack selectivity for the MC1R and thus can have side effects. The use of noncanonical amino acids in previous MC1R ligand development raises safety concerns. Here we report the development of the first potent and selective hMC1R agonist with only canonical amino acids. Using γ-MSH as a template, we developed a peptide, [Leu3, Leu7, Phe8]-γ-MSH-NH2 (compound 5), which is 16-fold selective for the hMC1R (EC50 = 4.5 nM) versus other melanocortin receptors. Conformational studies revealed a constrained conformation for this linear peptide. Molecular docking demonstrated a hydrophobic binding pocket for the melanocortin 1 receptor. In vivo pigmentation study shows high potency and short duration. [Leu3, Leu7, Phe8]-γ-MSH-NH2 is ideal for inducing short-term skin pigmentation without sun for melanoma prevention.
- Zhou, Yang,Mowlazadeh Haghighi, Saghar,Zoi, Ioanna,Sawyer, Jonathon R.,Hruby, Victor J.,Cai, Minying
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p. 9320 - 9329
(2017/11/30)
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- Des-Nalpha-acetyl-alpha-melanotropin: a synthetic substrate for specific N-terminal directed enzymatic acetylation.
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Application of the 2-methylsulfonylethyloxycarbonyl group for temporary amino protection enables the synthesis from one precursor of des-Nalpha1-acetyl-alpha-MSH, the two mono N-acetylated forms (in positions I and II) and the diacetyl form of this tridecapeptide amideq The free tridecapeptide amide, although structurally unrelated to the normal substrate, was recognized by an enzyme occurring in calf eye-lens tissue. The product of the enzymatic reaction was exclusively alpha-MSH. Partial sequences derived from the N-terminus were less rapidly acetylated or not at all, depending on their chain length. The enzyme, therefore, appears to direct its activity to free N-terminal alpha-amino groups of peptides exceeding a certain critical chain length. Acetylation of epsilon-amino functions did not occur.
- Smeets,Granger,Van Nispen,Bloemendal,Tesser
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