Change search
ReferencesLink to record
Permanent link

Direct link
3-(4-hydroxymethylphenylsulfanyl)propanoic acid (HMPPA) as a new safety catch linker in solid phase peptide synthesis
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0003-1003-6472
2006 (English)In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 32, no 7, 5829-5832 p.Article in journal (Refereed) Published
Abstract [en]

A new safety catch linker, 3-(4-hydroxymethylphenylsulfanyl)propanoic acid (HMPPA), is described for use in solid phase peptide synthesis. The linker is readily synthesized from commercially available chemicals in a more cost efficient way compared to similar reported linkers. The HMPPA linker is easily attached to an amino derivatized solid support followed by on-resin oxidation of the thioether to sulfoxide, thereby making the linker very stable towards strong acid treatment. Final resin cleavage is performed by reductive acidolysis.

Place, publisher, year, edition, pages
Elsevier Ltd , 2006. Vol. 32, no 7, 5829-5832 p.
National Category
URN: urn:nbn:se:su:diva-25838DOI: 10.1016/j.tetlet.2006.04.138OAI: diva2:200648
Available from: 2006-04-07 Created: 2006-04-07 Last updated: 2015-03-16Bibliographically approved
In thesis
1. Methodological studies in solid phase synthesis: Linkers and applications of multi-component condensations
Open this publication in new window or tab >>Methodological studies in solid phase synthesis: Linkers and applications of multi-component condensations
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Solid phase synthesis has become an increasingly important tool in the synthesis of oligopolymers and small organic molecules. This thesis covers three important areas in the solid phase synthesis technique: linker strategies, reduction methods and novel routes to complex heterocycles.

The synthesis of the OMPPA [4-(3-hydroxy-4-metylpentyl)phenyl acetic acid] linker is described. This linker is compatible with the Boc/Bzl protective group strategy, and yields peptide acids upon cleavage from solid support. The OMPPA linker is stable towards “low-acid” treatment and is self-scavenging during final cleavage of the peptide product from solid support. These properties are beneficial for peptide purity and yields.

The synthesis of the HMPPA [3-(4-hydroxymethylphenylsulfanyl)propanoic acid] linker is described. This safety catch linker is compatible with both Fmoc/tBu- and Boc/Bzl protective group strategies in solid phase peptide synthesis. The HMPPA linker is stable towards super acids yet final cleavage from solid support is performed by a relatively mild reductive acidolysis method, yielding peptide acids. It is suggested that this linker may be useful when synthesizing cyclic peptides on solid support. A new facile method for reducing cystine moieties is described. Adding metallic zinc to cystine containing peptides and proteins dissolved in slightly acidic aqueous and/or non-aqueous solutions, results in rapid disulfide reduction. This method is compatible with functional groups commonly present in peptides and proteins. The solid phase synthesis of oxygen-bridged tetrahydropyridones via a multi-component condensation reaction is described. Expected products were obtained in reasonable yields using both aromatic- and aliphatic ketones. This class of compounds has the general physico-chemical properties that are typical for drugs with high pharmacological activity.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2006. 87 p.
Solid phase peptide synthesis, solid phase organic chemistry, linkers, self-scavenging, safety catch linker, cyclic peptides, reductive acidolysis, disulfides, reduction, metallic zinc, multi-component condensations, combinatorial chemistry
National Category
urn:nbn:se:su:diva-922 (URN)978-91-7155-2 (ISBN)
Public defence
2006-04-27, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 13:00
Available from: 2006-04-07 Created: 2006-04-07Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Undén, Anders
By organisation
Department of Neurochemistry
In the same journal
Tetrahedron Letters

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 70 hits
ReferencesLink to record
Permanent link

Direct link