Coupling difficulty following replacement of Tyr with HOTic during synthesis of an analog of an EGF B-loop fragment.
During Fmoc synthesis of an analog, [Abu HOTic]hEGF(20-31), of a fragment, Cys-Met-Tyr-Ile-Glu-Ala-Leu-Asp-Lys-Tyr-Ala-Cys, of the B-loop of human EGF, conductivity measurements showed that increased time was necessary for coupling and complete deprotection of the residues Met and Abu which followed the HOTic. Use of different active esterforming reagents, including HOBt and BOP, did not increase the yield. Use of symmetrical anhydride with extended coupling time increased the yield but did not complete the coupling. It appears that inclusion of HOTic in place of Tyr to introduce conformational constrain to peptide analogs can cause or augment a tendency towards conformations with increasing occlusion of N-terminal amino groups and result in the need for altered coupling strategies for completion of analog synthesis.
Otvös
F
F
Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE 68178-0405, USA.
Murphy
R F
RF
Lovas
S
S
D000596:Amino Acids / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004815:Epidermal Growth Factor / Q000138:chemical synthesis*; D006801:Humans; D013058:Mass Spectrometry; D010452:Peptide Biosynthesis; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry*
D000596:Amino Acids; D014443:Tyrosine; D004815:Epidermal Growth Factor