Introduction of a tailor made anion receptor into the side chain of small peptides allows fine-tuning the thermodynamic signature of peptide–DNA binding

Li, Mao; Schlesiger, Stefanie; Knauer, Shirley K.; Schmuck, Carsten

doi:10.1039/c6ob01584k

Cited by 10 publications

(7 citation statements)

References 30 publications

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“…(Holliday junctions are cross-shaped structures formed by four double-stranded segments of DNA in which each DNA molecule participates in two segments(112)). An analysis of B-factors from X-ray crystal structures suggested that the most enthalpically favorable interactions (i.e., interactions involving highly polarizable anions) incurred strong entropic penalties that resulted from reduced intermolecular mobility.The observations of Freire, Klebe, Berg, and Ho (and many others(58,66,94)), are qualitatively consistent with the simplified description of H/S compensation initially proposed by Williams and Dunitz: When molecules bind tightly (favorable enthalpy), they incur conformational constraints (unfavorable entropy). This succinct description clearly helps rationalize some binding phenomena.…”

supporting

confidence: 84%

The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition

Fox

Zhao

Fink

et al. 2018

Annu. Rev. Biophys.

144

118

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Biomolecular recognition can be stubborn; changes in the structures of associating molecules, or the environments in which they associate, often yield compensating changes in enthalpies and entropies of binding and no net change in affinities. This phenomenon-termed enthalpy/entropy (H/S) compensation-hinders efforts in biomolecular design, and its incidence-often a surprise to experimentalists-makes interactions between biomolecules difficult to predict. Although characterizing H/S compensation requires experimental care, it is unquestionably a real phenomenon that has, from an engineering perspective, useful physical origins. Studying H/S compensation can help illuminate the still-murky roles of water and dynamics in biomolecular recognition and self-assembly. This review summarizes known sources of H/ S compensation (real and perceived) and lays out a conceptual framework for understanding and dissecting-and, perhaps, avoiding or exploiting-this phenomenon in biophysical systems.

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supporting

confidence: 84%

The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition

Fox

Zhao

Fink

et al. 2018

Annu. Rev. Biophys.

144

118

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“…Thus, the binding affinity of a series of tetrapeptides 34 ( a – e ) (Figure a) consisting of a different number of GCP and lysine residues was tested using calf thymus DNA (ctDNA). The results showed that binding became more enthalpy favored with an increasing number of GCP groups, compared to the free lysine residues (Figure b) . Therefore, the introduction of GCP moieties into the peptide could effectively alter the thermodynamic signature of peptide/DNA binding from an entropy driven process to an enthalpy driven one.…”

Section: Rational Design and Potential Application Of Gcp-based Molec...mentioning

confidence: 99%

Diverse Properties of Guanidiniocarbonyl Pyrrole-Based Molecules: Artificial Analogues of Arginine

Hatai

Schmuck

2019

Acc. Chem. Res.

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The guanidinium moiety, which is present in active sites of many enzymes, plays an important role in the binding of anionic substrates. In addition, it was also found to be an excellent binding motif for supramolecular chemistry. Inspired by Nature, scientists have developed artificial receptors containing guanidinium scaffolds that bind to a variety of oxoanions through hydrogen bonding and charge pairing interactions. However, the majority of binding studies is restricted to organic solvents. Polyguanidinium based molecules can form efficient complexes in aqueous solvents due to strong electrostatic interactions. However, they only have moderate association constants, which are significantly decreased in the presence of competing anions and salts. Hence, to improve the binding affinity of the guanidinium moiety, our group developed the cationic guanidiniocarbonyl pyrrole (GCP) moiety. This rigid planar analogue binds efficiently to oxoanions, like carboxylates even in aqueous solvents. The lower pK a value (7−8) of GCP compared to guanidinium derivatives (pK a 13) favors the formation of strong, hydrogen bonded ion pairs. In addition, carboxylate binding is further enhanced by additional amide hydrogen bond donors located at the five position of the pyrrole core. Moreover, the design has allowed for introducing secondary interactions between receptor side chains and guest molecules, which allows for optimizing binding specificity and selectivity. The spectroscopic data confirmed stabilization of guanidiniocarbonyl pyrrole/oxoanion complexes through a combination of ion pairing and multiple hydrogen bonding interactions. The key role of the ionic interaction in a polar solvent, is demonstrated by a zwitterion derivative of the guanidiniocarbonyl pyrrole, which self-assembles in both dimethyl sulfoxide and pure water with association constants of K > 10 10 M −1 and K = 170 M −1 , respectively. In this Account, we discuss strategies for making GCP functionalized compounds, in order to boost their ability to bind oxoanions. Then we explore how these building blocks have been incorporated into different synthetic molecules and peptide sequences, highlighting examples that demonstrated the versatility of this binding scaffold. For instance, the high oxoanion binding property of GCP-based compounds was exploited to generate a detectable signal for sensing applications, thus improving selectivity and sensitivity in aqueous solution. Moreover, peptides and molecules containing GCP have shown excellent gene transfections properties. Furthermore, the self-assembly and zwitterionic behavior of zwitterionic GCP analogues was used to develop variety of supramolecular architectures such as stable supramolecular β-helix structure, linear supramolecular oligomers, one-dimensional rods or two-dimension sheets, fibers, vesicles, soft nanospheres, as well as stimuli responsive supramolecular gels.

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“…3 The GCP-motif, which was developed by Carsten Schmuck, acts as a strong oxoanion-binder, so that especially its coupling to or combination with other cationic amino acids (such as lysine or arginine) has been important. The resulting GCP-lysine and GCParginine conjugates have been applied in anion-recoginition, 4,5,6 materials chemistry 7,8,9 and genetransfection. 10,11,12 To broaden the synthetic applicability of amino-acid derived building blocks, synthetic strategies other than the classical amide-coupling have been developed.…”

Section: Introductionmentioning

confidence: 99%

Triazole groups as biomimetic amide groups in peptides can trigger racemization

Hättasch¹,

Schmuck²,

Niemeyer³

2021

Arkivoc

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show abstract

Introduction of a tailor made anion receptor into the side chain of small peptides allows fine-tuning the thermodynamic signature of peptide–DNA binding

Cited by 10 publications

References 30 publications

The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition

The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition

Diverse Properties of Guanidiniocarbonyl Pyrrole-Based Molecules: Artificial Analogues of Arginine

Triazole groups as biomimetic amide groups in peptides can trigger racemization

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