<i>N</i>-Aminosulfamide Peptide Mimic Synthesis by Alkylation of Aza-sulfurylglycinyl Peptides

<i>N</i>-Aminosulfamides are peptidomimetics in which the C_αH and the carbonyl of an amino acid residue are both respectively replaced by a nitrogen atom and a sulfonyl group. Aza-sulfurylglycinyl tripeptide analogs were effectively synthesized from amino acid building blocks by condensations of <i>N</i>-protected amino hydrazides and <i>p</i>-nitrophenylsulfamidate esters. The installation of <i>N</i>-alkyl chains and access to other aza-sulfuryl amino acid residues were effectively achieved by chemoselective alkylation

<i>N</i>-Aminosulfamide Peptide Mimic Synthesis by Alkylation of Aza-sulfurylglycinyl Peptides

<i>N</i>-Aminosulfamides are peptidomimetics in which the C_αH and the carbonyl of an amino acid residue are both respectively replaced by a nitrogen atom and a sulfonyl group. Aza-sulfurylglycinyl tripeptide analogs were effectively synthesized from amino acid building blocks by condensations of <i>N</i>-protected amino hydrazides and <i>p</i>-nitrophenylsulfamidate esters. The installation of <i>N</i>-alkyl chains and access to other aza-sulfuryl amino acid residues were effectively achieved by chemoselective alkylation

Urotensin II^(4–11) Azasulfuryl Peptides: Synthesis and Biological Activity

Cyclic azasulfuryl (As) peptide analogs of the urotensin II (UII, <b>1</b>, H-Glu-Thr-Pro-Asp-<i>c</i>[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) fragment 4–11 were synthesized to explore the influences of backbone structure on biological activity. <i>N</i>-Aminosulfamides were inserted as surrogates of the Trp⁷ and Lys⁸ residues in the biologically relevant Trp-Lys-Tyr triad. A combination of solution- and solid-phase methods were used to prepare novel UII^(4–11) analogs <b>6</b>–<b>11</b> by routes featuring alkylation of azasulfuryl-glycine tripeptide precursors to install various side chains. The pharmacological profiles of derivatives <b>6</b>–<b>11</b> were tested <i>in vitro</i> using a competitive binding assay and <i>ex vivo</i> using a rat aortic ring bioassay. Although the analogs exhibited weak affinity for the urotensin II receptor (UT) without agonistic activity, azasulfuryl-UII^(4–11) derivatives <b>7</b>–<b>9</b> reduced up to 50% of the effects of UII and urotensin II-related peptide (URP) without affecting their potency