Engineered multivalent self-assembled binder protein against SARS-CoV-2 RBD

Engineered coiled-coil HIF1α protein domain mimic

“…Models for H-MAP solvent exposure were generated using Rosetta 19 and visualized in PyMOL. 20 A chain of the ACE-MAP PDB generated previously 17 was mutated in PyMOL after aligning the critical leucine residues in the HIF1α C-TAD with the critical ACE BINDER residues in ACE-MAP as determined by Lan et al 21 Rosetta Symmetry protocol 22 using symmetry defined from pdb:3V2P and FastRelax protocols with the REF2015 score function 23 were used to generate 200 poses and the top scoring pose was used as the model for H-MAP. H-MAP was further refined for increased solvent exposure by removing two alanines in the rigid linker section of the sequence and generating 200 poses using the Symmetry 22 and FastRelax protocols with the REF2015 score function 23 and using the best scoring pose.…”

“…We have previously designed a multivalent assembled protein (MAP) by fusion of the N-terminal α-helix of the human cell receptor protein ACE2 for recognition of the RBD of SARS-COV-2 utilizing a kinked rigid linker to the COMPcc domain. 17 We utilized this protein sequence as the foundation of new MAPs for inhibition of the HIF1α•p300 complex (H-MAP) (Fig. 1a).…”

“…Recently, we have established the use of a multivalent assembled protein (MAP) as a PDM against the SARS-CoV-2 receptor binding domain (RBD) by using the cartilage oligomeric matrix protein coiled-coil (COMPcc or C) domain as a fusion scaffold with the N-terminal α-helix of the ACE2 receptor (ACE BINDER ), 17 where entry of the virus is mediated. 18 C and ACE BINDER are separated by a rigid kinked linker to offer improved solvent exposure resulting in ACE-MAP.…”

“…18 C and ACE BINDER are separated by a rigid kinked linker to offer improved solvent exposure resulting in ACE-MAP. 17 ACE-MAP exhibits the ability to self-assemble into a pentamer, offers high thermostability and improved binding affinity to the native ACE2 protein.…”

Amphiphilic α-Peptoid-deoxynojirimycin Conjugate-based Multivalent Glycosidase Inhibitor for Hypoglycemic Effect and Fluorescence Imaging

“…Multivalent interactions are widespread in nature and play important roles in biological processes, − such as cell adhesion, growth regulation, , bacterial and viral infections, − immune regulation and response, and DNA transcription . Multivalent carbohydrate–protein interactions are the key processes in a plethora of critical biological functions, − including the adhesion of the influenza virus to cell membranes, the targeting cell recognition of carbohydrates with membrane receptors, − and the immune response of carbohydrates with macrophages and dendritic cells. − Novel therapeutic drugs based on multivalent carbohydrate–protein interactions have seen rapid development and clinical application in recent years, such as GalNAc-siRNA for hepatic targeting with the asialoglycoprotein receptor (ASGPR) − and lysosome-targeting chimera (LYTAC) technology based on mannose-6-phosphate and GalNAc derivatives.…”