Protocol for efficient solid-phase synthesis of peptides containing 1-hydroxypyridine-2-one (1,2-HOPO)

Danah Al Shaer; Beatriz G de la Torre; Fernando Albericio

doi:10.1016/j.mex.2020.101082

Protocol for efficient solid-phase synthesis of peptides containing 1-hydroxypyridine-2-one (1,2-HOPO)

MethodsX. 2020 Sep 28:7:101082. doi: 10.1016/j.mex.2020.101082. eCollection 2020.

Authors

Danah Al Shaer^{1

2}, Beatriz G de la Torre¹, Fernando Albericio^{2

3

4}

Affiliations

¹ 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.
² Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa.
³ Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain.
⁴ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine and Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain.

Abstract

•Metal chelation has found many applications that directly affect human's life.•Natural siderophores are one of the most potent chelators for Fe (III)•1-Hydroxypyridine-2-one (1,2-HOPO) (Fig. 1a), which is shown in 4-carboxy-1-hydroxypyridin-2-one (1,2-HOPO-4-COOH) (Fig. 1b), is a moiety that electronically resembles the hydroxamate group found in natural siderophores (Fig. 1c). Of note, 1,2-HOPO moiety is present in the natural siderophore cepabactin [1]•Synthesis of 1,2-HOPO containing chelators has been carried in solid phase using carboxylic acid derivatives of 1,2-HOPO and required the protection of the reactive hydroxyl group usually with benzyl group (Bzl). After the peptide elongation, the Bzl group has been removed on the same solid phase using a bit harsh conditions: 0.1 M BBr₃ in DCM for 60 min [2], 10% HBr in AcOH for 14 h [3]; in solution: 1 M BCl₃ in DCM for 2 d [4], 50% HCl in AcOH for 4 d [5], H2-Pd/C, AcOH-MeOH [6].•First of all, a method for the incorporation of the 1,2-HOPO-4-COOH through its carboxyl group into the peptide backbone without protecting the N-OH is proposed (the presence of the carboxyl group facilitates the attachment).•Furthermore, in the cases that Bzl protection is required for the N-OH, a friendlier method for removing the Bzl is described. The removal of the Bzl is done concomitantly to the global deprotection and cleavage of the peptide from the resin using TFA- TFMSA-H₂O (8:3:1).

Keywords: 1-Hydroxypyridine-2-one; Fe (III) chelators; Siderophores; Solid phase peptide synthesis; Trifluoromethanesulfonic acid (TFMSA).