Abstract
Proline with its unique geometrical feature generates turn in the peptide backbone. Therefore, aggregation potential of Aβ38 can be modulated by insertion of proline at specific positions. Although site specific proline mutation is reported, effect of multiple proline substitution on aggregation potential is still not demonstrated. Therefore, Aβ38, a single proline substituted variant, V18P-Aβ38, a double proline substituted variant, V18P-I31P-Aβ38 and a triple proline substituted version, V12P-V18P-I31P-Aβ38 were synthesized and their aggregation potential were studied. The proline mutants found to have higher solubility and slower aggregation kinetics. The double mutated version was relatively less aggregation prone than its single mutated version. Such analogues can be useful for designing new β sheet breaker peptides, studying the mechanism of aggregation and structural analyses.
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Acknowledgements
We are thankful to CIF, IITG for TEM studies, Mr. Sameer Hussain and Prof. P. K. Iyer for their help in birefringence studies, Mr. Mohitosh Dey and Prof. S. S. Ghosh for their help in CD studies, reviewers for constructive suggestions and BRNS DAE (2008/20/37/6/BRNS) for financial support.
Conflict of interest
Nadimpally Krishna Chaitanya, Ashim Paul, Abhijit Saha and Bhubaneswar Mandal declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects.
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Chaitanya, N.K., Paul, A., Saha, A. et al. Modulation of Aggregation Propensity of Aβ38 by Site Specific Multiple Proline Substitution. Int J Pept Res Ther 19, 365–371 (2013). https://doi.org/10.1007/s10989-013-9360-1
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DOI: https://doi.org/10.1007/s10989-013-9360-1