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Synthetic polyamines: an overview of their multiple biological activities

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Abstract

The binding of polyamines to a variety of receptors and other defined recognition sites has been widely reported. It is well-known that polyamines interact with aspartate, glutamate, and aromatic residues of a given receptor and/or enzyme mainly through the formation of ion bonds, since at physiological pH, protonation of amino groups is nearly complete. From this, the hypothesis arises that a polyamine may be a universal template able to recognize different receptor systems. This hypothesis suggests that both affinity and selectivity may be fine-tuned by inserting appropriate substituents onto the amine functions and by varying the methylene chain lengths between them on the polyamine backbone. In this paper, we detail several application of this design strategy aimed at discovering potent and selective polyamines able to bind neurotransmitter receptors and enzymes, such as muscarinic receptor subtypes, muscle-type nicotinic receptors and acethylcholinesterase.

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Abbreviations

SAR:

Structure–activity relationship

4-DAMP:

4-diphenylacetoxy-N-methylpiperidine

nAChR:

Nicotinic receptor

PhTX-433:

Philanthotoxin-433

AD:

Alzheimer’s disease

Aβ:

β-amyloid

AChE:

Acetylcholinesterase

ACh:

Acetylcholine

PAS:

Peripheral anionic site

MTDL:

Multi-target-directed ligand

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Acknowledgments

This research was supported by a grant from MIUR, Rome (PRIN).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy

    Anna Minarini, Andrea Milelli, Vincenzo Tumiatti, Michela Rosini, Maria Laura Bolognesi & Carlo Melchiorre

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  1. Anna Minarini
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  2. Andrea Milelli
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  3. Vincenzo Tumiatti
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  4. Michela Rosini
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  5. Maria Laura Bolognesi
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  6. Carlo Melchiorre
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Correspondence to Anna Minarini.

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Minarini, A., Milelli, A., Tumiatti, V. et al. Synthetic polyamines: an overview of their multiple biological activities. Amino Acids 38, 383–392 (2010). https://doi.org/10.1007/s00726-009-0430-9

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