NDLI: Supramolecular guest relay using host-protein nanocavities: an application of host-induced guest protonation

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chandra, Falguni Pal, Kaushik Lathwal, Sushil Koner, Apurba L.
Description	Country affiliation: India Author Affiliation: Chandra F ( Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal, India. akoner@iiserb.ac.in.); Pal K ( Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal, India. akoner@iiserb.ac.in.); Lathwal S ( Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal, India. akoner@iiserb.ac.in.); Koner AL ( Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal, India. akoner@iiserb.ac.in.)
Abstract	Small drug molecules and other important metabolites are delivered via a suitable carrier protein-mediated transport through a specific receptor. The process is highly coordinated and associated with complexation induced properties of deliverable molecules. To get a molecular insight, in this report, we tried to mimic the delivery process to know how the carrier protein relocates the drug molecule from the macrocyclic host cavity to its binding pocket and how the electronic and the chemical properties of the guest get altered. Bovine and human serum albumin (BSA and HSA) were used as the model carrier proteins which can snatch out 6-propanoyl-2-(N,N-dimethylamino)naphthalene (PRO), dye used as a drug model (known to bind at the drug-binding pocket of the carrier protein), from the cucurbit[7]uril (CB7) cavity, a potential drug delivery carrier. Prior to performing the fluorescence-based bio-supramolecular relocation assay using BSA and HSA, CB7 and PRO, we have investigated the effect of CB7 encapsulation and protonation on the fluorescence properties of PRO. A significant shift in the $pK_{a}$ value from 3.4 to 6.6 (ca. 3.2 logarithmic units) of PRO was observed upon encapsulation with CB7, which causes a huge fluorescence quenching even at neutral pH. The binding affinity of protonated and neutral PRO for CB7 also confirms a 3.2 unit shift in the acid-dissociation constant. A displacement assay using a strong CB7 binder, viz., 1,6-diaminohexane, confirms encapsulation of PRO in the CB7 cavity. Encapsulation of neutral PRO by CB7 shows a significant fluorescence enhancement accompanied by a ∼35 nm blue shift in the emission maxima.
File Format	HTM / HTML
ISSN	1742206X
Issue Number	9
Journal	Molecular BioSystems
Volume Number	12
e-ISSN	17422051
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-08-16
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in