1-Hydroxybenzotriazole as a racemization-suppressing reagent for the incorporation of im-benzyl-L-histidine into peptides

Windridge, Graham C.; Jorgensen, Eugéne C.

doi:10.1021/ja00752a081

Cited by 86 publications

(27 citation statements)

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“…Rf 0.64 (b). Total hydrolysis with HCl/propionic acid and mercaptoethanesulfonic acid, 110", 24h, of a sample and amino acid analysis gave an amino acid content which was in agreement with the theory: Arg 1.01 (l), Gly 1.00 (l), Ser 0.96 (l), Leu 0.93 (l), Pro 1.00 (l), Tyr 0.93 (1) and Trp 1.82 (2).…”

Section: Isolation and Purification Of Boc-trp-ser(bz1)-tyr(bz1)-d-trsupporting

confidence: 84%

Histidine racemization in the synthesis of an analog of the lutenizing hormone releasing factor

Pipkorn

Ekberg

1986

International Journal of Peptide and Protein Research

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To investigate histidine racemization in the synthesis of a LHRH analog, (D‐Trp)6‐LHRH2–10 was built up by stepwise elongation of the sequence 3–10 using the solid phase technique on a 1% cross‐linked chloromethyl polystyrene. For the whole synthesis the tert.‐butyloxycarbonyl (BOC) group was used for temporary N‐terminal protection. To protect the π‐nitrogen in histidine the benzyloxymethyl (BOM) group was utilized. The condensation position in the (D‐Trp)6‐LHRH analog was chosen so as to be able to investigate the racemization of histidine. We coupled BOC‐His(BOM) with the (D‐Trp)6‐LHRH3–10 fragment using three different activating agents, mixed anhydride, carbonyldiimidazole (1 equiv.)/1‐hydroxybenzotriazole (2 equiv.) and dicyclohexylcarbodiimide/1‐hydroxybenzotriazole. The racemization was investigated by enzymatic digestion and by HPLC. For HPLC, (D‐His(BOM)2‐(D‐Trp)6‐LHRH2–10 was also synthesized. It could be proved that practically no racemization occurs during the actual peptide synthesis. The small amount (1%) of D‐histidine found is due to racemization in the synthesis of BOC‐His(BOM).

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Section: Isolation and Purification Of Boc-trp-ser(bz1)-tyr(bz1)-d-trsupporting

confidence: 84%

Histidine racemization in the synthesis of an analog of the lutenizing hormone releasing factor

Pipkorn

Ekberg

1986

International Journal of Peptide and Protein Research

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“…Based on previously described procedures (König & Geiger, 1970;Windridge & Jorgensen, 1971;Carpino & El-Faham, 1999), the active ester HOBt was applied in the combination with carbodiimides. This approach was modified for silicone oils as has recently been published by our research group (Partenhauser et al, 2015).…”

Section: Synthesis and Purification Of Thiolated Silicone Oilmentioning

confidence: 99%

Evaluation of thiolated silicone oil as advanced mucoadhesive antifoaming agent

et al. 2015

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Context: Silicone oils, such as dimethicone, are commonly administered against gastrointestinal gas accumulation and are attributed with mucoprotective features. Objective: Evaluation of thiolated silicone oil as advanced antiflatulence with a prolonged retention on small intestinal mucosa as an intended site of action. Materials and methods: 3-Mercaptopropionic acid (MPA) as a thiol ligand was covalently attached to silicone oil. This thiomer was assessed with regard to foam inhibiting action, droplet size of a suitable self-emulsifying system, mucoadhesion and cytotoxicity. Results: Antifoaming activity of silicone-MPA was complying with United States Pharmacopeia (USP) requirements for simethicone as standard antiflatulence. Another antifoaming test performed on porcine mucosa supported silicone-MPA's outstanding foam destruction, as this thiomer was superior in comparison to non-thiolated silicone oil and dimethicone with 14.7 ± 2.1 versus 73.3 ± 9.1 and 66.3 ± 7.5 s, respectively. A significantly enhanced mucoadhesiveness (p50.02) with 26.2 ± 7.1% silicone formulation remaining on small intestinal mucosa after 8 h was evident for the thiomer without any toxic effect. Conclusion: Thiolated silicone oil was found to exhibit excellent antifoaming and superior mucoadhesive features. The prolonged residence time of thiolated silicone oil promises to be beneficial in the treatment of flatulence, aerophagy and inflammation throughout the whole gastrointestinal tract.

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“…Thus, in the synthesis of Z-Pro-Val-Pro-OBu-t, it was found that the amount of racemic product is 9%. 83 However, in most cases racemisation was not observed, and, what is also important, the yields of peptides in the presence of added 1-hydroxybenzotriazole were higher than in the presence of Nhydroxysuccinimide.…”

Section: Rcoo -mentioning

confidence: 98%