Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.

The present invention relates to compositions comprising RNA, preferably messenger RNA (mRNA), more preferably self-amplifying RNA (saRNA), and polymers, in particular cationic polymers, such as polyethylenimine (PEI), poly-L-Lysin (PEL), polyvinylamine (PVA) or polyallylamine (PAA), where individual RNA molecules are present in solution. In the formulations, the RNA is preferentially present in the form of monomers, dimers, timers or oligomers, but not as aggregates comprising a large number of RNA molecules per aggregate, in particular large polyplex nanoparticles. The formulations display improved transfection efficacy and they can be used for delivery of RNA to a subject, where they have an improved dose response relationship in comparison to formulations where large aggregates in the form of polyplex nanoparticles are present.

The present disclosure relates to nucleic acid-peptide-nucleic acid conjugate molecules and to methods for synthesizing nucleic acid-peptide-nucleic acid conjugate molecules. In some embodiments, a method for synthesizing a nucleic acid-peptide-nucleic acid conjugate molecule using proximity-enhanced synthesis includes covalently linking a peptide with a first nucleic acid strand via a first reaction, hybridizing the first nucleic acid strand with a second nucleic acid strand to bring the second nucleic acid strand in proximity to the peptide, and covalently linking the peptide with the second nucleic acid strand via a second reaction to provide the nucleic acid-peptide-nucleic acid conjugate molecule. In some embodiments, the peptide of the nucleic acid-peptide-nucleic acid conjugate molecule is a substrate for cleavage by an enzyme, such as matrix metalloproteinase-8 (MMP-8). Exemplary applications of the nucleic acid-peptide-nucleic acid conjugate molecule for drug delivery, molecular assembly of hybrid structures, and constraining the peptide to a biologically active conformation are also disclosed.

A first derivative of a fullerene is covalently bonded to an adenosine phosphate such as adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, or cyclic adenosine monophosphate. A second fullerene is covalently bonded to a second type of functional group including amines of arginine and lysine. The second fullerene is then van-der-Waals bonded to the first fullerene, to form a biaxially pivoting fullerene molecular composition. This composition can be treated to intercalate and carry a drug or an antibody for later release by directed irradiation. The injected composition with optional drug carrier is electrodynamically activated by irradiation of the injected target organ or tissues by the application of, for example, radio frequency (RF) energy to release the drug and lyse the targeted cells.

Senolytic and anti-inflammatory prodrugs are provided, which are designed from a cytotoxic agent, by chemically modifying the cytotoxic agent to incorporate a site cleavable by SA-β-gal following delivery of the prodrug in vivo, to release the active parent drug. The prodrug includes a galactose-based moiety, which is preferably acetylated, and benzyl oxy carboxy group and a cytotoxic agent moiety. The selenolytic prodrug is used to selectively kill one or more senescent cells and/or reduce an acute or chronic inflammatory response in a subject in need thereof, by administering to the subject therapeutically effective amount of the senolytic prodrugs. The disclosed compositions can be used to reduce one or more symptoms associated with a Senescence-associated disease or disorder or an inflammatory disorder, for example, a virus-mediated inflammation, in a subject.

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.

Provided herein are glycosylated peptide amphiphiles (GPAs), supramolecular glyconanostructures assembled therefrom, and methods of use thereof. In particular, provided herein are glycosaminoglycan (GAG) mimetic peptide amphiphiles (PAs) and supramolecular GAG mimetic nanostructures assembled therefrom that mimic the biological activities of GAGs, such as heparin, heparan sulfate, hyaluronic acid etc.

The present disclosure relates generally to antibody-drug conjugates comprising peptide-containing linkers and to methods of using these conjugates as therapeutics and/or diagnostics. Also disclosed herein are peptide-containing scaffolds useful to conjugate with a targeting moiety (e.g., an antibody), a drug, or both to produce the antibody-drug conjugates.

The present disclosure relates to the field of pharmaceutical chemistry, and particularly to a compound represented by Formula (I), a preparation method and medical use thereof. In the compound represented by Formula (I), a lactulosyl group is connected to a heteroatom of genin (G) via a glycosidic bond, wherein the genin (G) is a group formed by removing one hydrogen atom from a heteroatom of an active pharmaceutical molecule, and “” indicates that the lactulosyl group is connected to the heteroatom of the genin (G) via an α-glycosidic bond or a β-glycosidic bond. Pharmacokinetic experiments prove that the lactuloside compound according to the present disclosure can pass through the gastrointestinal tract of a mammal without being absorbed significantly by the gastrointestinal tract and hydrolyzed significantly by endogenous enzymes of a mammal host. Therefore, the lactuloside compound can arrive at the colon site of the mammal, and release an active drug in the colon under the action of colon flora. The lactuloside compound has a function of colon-localized drug release, and can be used for preventing or treating an intestinal disease. ##STR00001##

This disclosure related to modular and programmable peptide-oligonucleotide chimeras comprising of peptide and oligonucleotide segments interlinked by an organic core are presented and their assembly as morphologically-tunable soft materials, for example, nanostructure compositions comprising a plurality of compounds comprising a peptide segment and an oligonucleotide segment interlinked by an organic core moiety.