Multivalency

11Multivalent Calixarenes for the Targeting of Biomacromolecules

Francesco Sansone and Alessandro Casnati

Department of Chemistry, Life Sciences and Environmental Sustainability, Università di Parma, Parco Area delle Scienze 17/a, 43124, Parma, Italy

11.1 Introduction

Multivalency [1] is an extremely powerful concept in supramolecular chemistry, nanotechnology and bioorganic chemistry since it allows not only to reinforce binding, but also to make it more specific [2–5]. In fact, the multiple presentation of several binding/ligating units (epitopes) properly arranged on a main scaffold might result in multivalent ligands possessing a much higher affinity (lower dissociation constant, K_D) than that of a single ligating unit. For an efficient binding, the design of the multivalent ligands is extremely important since the number, the distance between the ligating units and the flexibility of the linkers which connect them to the scaffold deeply influence the overall binding energy with the target receptor. This effect, also called the multivalent effect, is generally attributed to an entropic gain originated by a high local concentration and a high statistical (re)binding probability of the ligating groups that, after the first intermolecular binding event, result in close proximity to the receptor sites. Multivalency is also quite often used by nature to make recognition events more efficient and selective [1].

Calix[n]arenes (Figure 11.1, 1: n ≥ 4) [6–11] are the cyclic oligomers ...