Evidence for Quantum Chemical Effects in Receptor-Ligand Binding Between Integrin and Collagen Fragments — A Computational Investigation With an Impact on Tissue Repair, Neurooncolgy and Glycobiology

Abstract

The collagen-integrin interactions are mediated by the doubly charged Mg2+ cation. In nature this cation seems to have the optimal binding strength to stabilize this complex. It is essential that the binding is not too weak so that the complex becomes unstable, however, it is also of importance that the ligand-receptor binding is still labile enough so that the ligand can separate from the receptor in a suited environment. In the case of crystal growing for experimentally useful integrin-collagen fragment complexes it turned out that Co2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co2+ is in this context an artificial cation, however, it is now of special interest to test the impact of this cation in cell-culture experiments focusing on integrin-ligand interactions. In order to examine, in particular, the role cobalt ions we have studied a Co2+ based model system using quantum chemical calculations. Thereby, we have shown that hybrid and long-range corrected functional, which are approximations provide already a sufficient level of accuracy. It is of interest to study a potential impact of cations on the binding of collagen-fragments including collagens from various species because different integrins have numerous biological functions (e.g. Integrin – NCAM (Neural cell adhesion molecule) interactions) and are triggered by intact and degraded collagen fragments. Since integrin–carbohydrate interactions play a key role when bio-medical problems such as tumor cell adhesion and virus-host cell infections have to be addressed on a sub-molecular level it is essential to understand the interactions with heavy-metal ions also at the sub-atomic level. Our findings open new routes, especially, in the fields of tissue repair and neuro-oncology for example for cell-culture experiments with different ions. Since Co2+ ions seem to bind stronger to integrin than Mg2+ ions it should be feasible to exchange these cations in suited tumor tissues although different cations are present in other metalloproteins which are active in such tissues. Various staining methods can be applied to document the interactions of integrins with carbohydrate chains and other target structures. Thereby, it is possible to study a potential impact of these interactions on biological functions. It was therefore necessary to figure out first which histological–glycobiological experimental settings of tumor cells are suited for our purpose. Since the interactions of several metalloproteins (integrin, ADAM12) with polysialic acid and the HNK-1 epitope play a crucial role in tumor tissues selected staining methods are proper tools to obtain essential information about the impact of the metal ions under study.

Preparation, Characterization, Evaluation of Neuroprotective Effect, and Related Mechanisms of Phosphatidylserine Emulsion in 5- and 12-Week Old Mice

“…The emulsion is a thermodynamically unstable system, which mainly has problems with physical instability. , Thus, improving emulsion physical stability against gravitational separation and droplet aggregation has attracted much more interest. Beside health benefits in food administration, our results also provide important insights when peptide- and protein-based drugs have to be encapsulated for an oral use in a clinical context. − …”

Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms

“…Answers to biomedical questions provided by tools applied in the field of nanomedicine such as quantum-chemical/DFT calculations on collagen-integrin interactions [89], as well as neuronal research related to sialic acids [20] and studies on the lectin-like function human lysozyme [7,8] may provide valuable hints for the direction of treatment options to curtail the SARS-CoV-2 pandemic. In a recent publication (retrospective study [90]), it was reported that incretin mimetics used in TD2 diabetes therapy had no effect on COVID-19-related symptoms in diabetic patients under incretin treatment infected by SARS-CoV-2.…”

“…In previous publications, we demonstrated that, in addition to a binding affinity to sialic acid moieties, a specific binding to sulfated carbohydrates is also important to establish stable ligand receptor complexes which are related to so-far non-answered biomedical questions [91][92][93]. Furthermore, ab initio and DFT quantum-chemical calculations are necessary to obtain the nanomedical details of these affinities since they may depend on certain functional groups or conformational states [94,95] as well as on the stabilizing cations involved [89].…”