The present invention relates to compositions comprising a delivery vehicle conjugated to a targeting domain, wherein the delivery vehicle comprises at least one agent, and wherein the targeting domain specifically binds to an CD4.sup.+ T cell antigen. The invention also relates to methods of treating or preventing diseases and disorders, including cancers, infectious diseases, and immunological disorders, using the described compositions.

The present disclosure provides macrocyclic compounds inspired by the immunophilin ligand family of natural products FK506 and rapamycin. The generation of a Rapafucin library of macrocyles that contain FK506 and rapamycin binding domains should have great potential as new leads for developing drugs to be used for treating diseases.

The present disclosure relates to base-editing systems including a fusion protein including a DNA-binding domain and a cytidine deaminase domain and a non-protein uracil-DNA glycosylase inhibitor, and methods of using the same. The DNA-binding domains of base-editing systems of the present disclosure include domains with a variety of target region possibilities, which increase the number and type of sequences that can be edited. The npUGIs of the base-editing systems of the present disclosure improve UDG inhibition (e.g., UDG inhibition is more complete) and are suitable for use in a wide range of organisms.

Compounds of Formula IA, IB, II, III, IV, and/or V are described herein along with their methods of use. A compound of the present invention may cross-link under physiological conditions and/or in vivo.

Ucn2 derivatives comprising a peptide and a substituent with high potency, high physical and high chemical stability, suitable for administration to humans, and their medical use in treatment and/or prevention of obesity and/or diabetes.

Immunogen enhancers for admixture with an antigen of interest are described herein. The enhancers generally comprise a steroid acid and/or a steroid acid-peptide conjugate in an amount sufficient to improve or modify the adaptive immune response to antigens admixed therewith. In embodiments, the steroid acid may be a bile acid and the peptide may comprise one or more functional domains, such as a nuclear localization signal, which may facilitate antigen-presentation and/or antigen cross-presentation, thereby triggering improved cellular immunity, or improved cellular and humoral immunity, against the antigen.

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

A method for treating psoriasis including the steps of applying an isothiocyanate functional surfactant to an area affected by psoriasis, wherein the isothiocyanate functional surfactant comprises at least one isothiocyanate functional group associated with an aliphatic and/or aromatic carbon atom of the isothiocyanate functional surfactant.

The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.