Polar Amino Acids for Increased Solubilization

Published on 21/11/2014

alpha-Sulfo-beta-Alanine has been used to couple to hydrophobic molecules and peptides and increase solubility. Attachment can be carried out by conventional Fmoc/tBu protocols.

alpha-Sulfo-beta-Alanine has been used to couple to hydrophobic labels like Cyanine and Rhodamine dyes and other hydrophobic residues to increase their solubility in water. As di- or tripeptide a further increase of hydrophilicity can be achieved. Fmoc-beta-Ala(SO3H)-OH (FAA1915) can be coupled in SPPS by standard phosphonium or uronium based coupling reagents. In high throughput technologies for DNA sequencing and genomics, charge-modified dye-labeled dideoxynucleoside-5’- triphosphates were synthesized for ‘direct-load’ applications in DNA sequencing.

Polar Amino acids for increased solubilisation

A di- or tripeptide fragment can be used in Antibody-Drug-Conjugation (ADC) to increase solubility in particular whenever hydrophobic peptide fragments are desired such as the Ala-Leu-Ala-Leu and Gly-Phe-Leu-Gly motif. Antibody conjugates with hydrophilic spacers are showing clearly higher solubilty than with hydrophobic residues, only.

References:

New insights into the water-solubilization of thiol-sensitive fluorogenic probes based on long-wavelength 7-hydroxycoumarin scaffolds; B. Roubinet, P.-Y. Renard and A. Romieu; Dyes and Pigments 2014; 110: 270-284. doi:http://dx.doi.org/10.1016/j.dyepig.2014.02.004
N-Fmoc-alpha-sulfo-beta-alanine: a versatile building block for the water solubilisation of chromophores and fluorophores by solid-phase strategy; A. Romieu, T. Bruckdorfer, G. Clave, V. Grandclaude, C. Massif and P.-Y. Renard; Organic & Biomolecular Chemistry 2011; 9: 5337- 5342. doi:10.1039/c1ob05730h
Water solubilization of xanthene dyes by post-synthetic sulfonation in organic media; A. Romieu, D. Tavernier-Lohr, S. Pellet-Rostaing, M. Lemaire and P.-Y. Renard; Tetrahedron Letters 2010; 51: 3304-3308. doi:http://dx.doi.org/10.1016/j.tetlet.2010.04.080
Water-Soluble BODIPY Derivatives; S. L. Niu, G. Ulrich, R. Ziessel, A. Kiss, P.-Y. Renard and A. Romieu; Org Lett 2009; 11: 2049-2052. doi:10.1021/ol900302n
Postsynthetic Derivatization of Fluorophores with α-Sulfo-β-alanine Dipeptide Linker. Application to the Preparation of Water-Soluble Cyanine and Rhodamine Dyes; A. Romieu, D. Brossard, M. Hamon, H. Outaabout, C. Portal and P.-Y. Renard; Bioconjug Chem 2007; 19: 279- 289. doi:10.1021/bc7003268