2. Academic Validation
  3. Improving 2-Chlorotrityl Chloride (2-CTC) Resin Activation

Improving 2-Chlorotrityl Chloride (2-CTC) Resin Activation

  • Methods Protoc. 2023 Sep 8;6(5):82. doi: 10.3390/mps6050082.
Tanya Román 1 2 3 4,  Gerardo Acosta 3 4,  Beatriz G de la Torre 5,  Constanza Cárdenas 1,  Fanny Guzmán 1,  Fernando Albericio 3 4 6
Affiliations

Affiliations

  • 1 Núcleo Biotecnología Curauma, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile.
  • 2 Doctorado en Biotecnología, Pontificia Universidad Católica de Valparaíso, Universidad Técnica Federico Santa María, Valparaíso 2373223, Chile.
  • 3 Department of Organic Chemistry and CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, University of Barcelona, 08028 Barcelona, Spain.
  • 4 Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain.
  • 5 KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
  • 6 Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Westville, Durban 4000, South Africa.
PMID: 37736965 DOI: 10.3390/mps6050082
Abstract

Used in solid-phase peptide synthesis (SPPS) for peptides with an acid termination, the 2-chlorotrityl chloride (2-CTC) resin is highly susceptible to Moisture, leading to reduced resin loading and lower synthetic yields. It is therefore recommended that the resin be activated with thionyl chloride (SOCl2) before peptide assembly. Here we present an optimized procedure for resin activation that minimizes the use of SOCl2 as the activation reagent and reduces the activation time. Additionally, we demonstrate the feasibility of reusing the 2-CTC resin when following the activation protocol, achieving comparable results to the first usage of the resin. Moreover, we achieved different degrees of resin activation by varying the amount of SOCl2. For instance, the use of 2% SOCl2 in anhydrous dichloromethane (DCM) allowed up to 44% activation of the resin, thereby making it suitable for the synthesis of longer peptides. Alternatively, employing 25% SOCl2 in anhydrous DCM resulted in up to 80% activation with a reaction time of only 5 min in both cases.

Keywords

2-CTC resin activation; 2-CTC resin reutilization; resin loading; solid-phase peptide synthesis.

Figures
Products