Pre-proofs are now available for our latest manuscript in Carbohydrate Polymers: “Addressing the complexities in measuring cyclodextrin-sterol binding constants: A multidimensional study”.
Abstract:
Cyclarity Therapeutics has developed a new class of cyclodextrin (CD) dimers as a potential new treatment for atherosclerosis. These CD therapies work by forming strong, soluble inclusion complexes with oxysterols, allowing the body to reduce and heal arterial plaques. However, characterizing the interactions between CD dimers and oxysterols presents formidable challenges due to low sterol solubility, the synthesis of modified CDs resulting in varying number and position of molecular substitutions, and the diversity of interaction mechanisms. To address these challenges and illuminate the nuances of CD-sterol interactions, we have used multiple orthogonal approaches for a comprehensive characterization. Results obtained from three independent techniques – metadynamics simulations, competitive isothermal titration calorimetry, and circular dichroism – to quantify CD-sterol binding are presented. The objective of this study is to obtain the binding constants and gain insights into the intricate nature of the system, while accounting for the advantages and limitations of each method. Notably, our findings demonstrate ~1000× stronger affinity of the CD dimer for 7-ketocholesterol in comparison to cholesterol for the 1:1 complex in direct binding assays. These methodologies and findings not only enhance our understanding of CD dimer-sterol interactions, but could also be generally applicable to prediction and quantification of other challenging host-guest complex systems.
Congratulations to our team and collaborators – great work!
About Cyclarity
Cyclarity Therapeutics, Inc., is pursuing a mission to treat the underlying causes of age-related disease. The company develops simple and direct interventions targeting oxidized cholesterol using rationally designed molecules, to provide the first true disease-modifying treatments for common age-related conditions such as atherosclerosis, heart attack and stroke. Its products are based on novel derivatives of a well-known, safe compound and a new way of looking at cardiovascular disease. For more information, please visit www.cyclaritytx.com or send an email to press@cyclaritytx.com
Forward Looking Statements
The information and statements contained herein contain forward-looking statements, which are subject to risks and uncertainties that could cause actual results to differ materially from such forward-looking statements and should not be considered as an indication or guarantee of future performance. Forward-looking statements involve known and unknown risks and uncertainties which could cause the Company’s prospects or actual results to differ materially from those in the forward-looking statements. The Company does not undertake any obligation to update the information or forward-looking statements contained herein whether as a result of new information or future events or otherwise.
Contact:
Mike Kope
CEO of Corporate Affairs
Cyclarity Therapeutics, Inc.
press@cyclaritytx.com
