An ultrasound-assisted simulated digestion method of a milk protein active peptide and an application thereof in health foods, pertaining to the technical field of intensive processing of dairy products and preparation of health foods. The method firstly employs ultrasonic pretreatment of casein and β-lactoglobulin, followed by enzymatic hydrolysis with a protease to prepare casein and ρ-lactoglobulin polypeptide, and traces the activity of the polypeptide by simulating gastrointestinal digestion, and then simulates absorption by intestinal epithelial cells with Caco-2 cells, to characterize a highly active milk protein polypeptide digested by the gastrointestinal tract and absorbed by the Caco-2 cells simulating absorption by the inner wall of the small intestine. The method has identified five such highly active milk protein polypeptides.

The present invention provides compounds of formula (I) ##STR00001## wherein X, L.sup.1 and R.sup.1 to R.sup.10 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments for the treatment of diseases and infections caused by Acinetobacter baumannii.

An object of the present invention is to provide a method for measuring tryptase activity in a blood sample accurately and rapidly by a convenient operation in order to accurately evaluate the state of a disease whose state involves mast cells. The present invention enables tryptase activity in a blood sample to be directly measured without the pretreatment, such as purification or concentration, of the blood sample, using a substrate for measuring tryptase activity, comprising a tripeptide C-terminally linked through a peptide bond to a dye label, selected from the following formulas (1) to (3): (1) Lys-Ala-Arg-X, (2) Ala-Ala-Arg-X, and (3) Abu-Ala-Arg-X (wherein X represents a dye label whose fluorescence characteristics or color development characteristics change upon the cleavage of the peptide bond with Arg, and Abu represents 2-aminobutyric acid).

A heterobifunctional monodisperse polyethylene glycol with two adjacent monodisperse polyethylene glycol side chains, in which a peptide linker is degraded by intracellular enzymes to release a drug slowly and effectively mask the hydrophobicity of the drug, and an antibody-drug conjugate in which the antibody and the drug are bound using same is provided. A heterobifunctional monodisperse polyethylene glycol represented by the formula (1):

##STR00001##

wherein each symbol in the formula (1) is as defined in the DESCRIPTION.

An ultrasound-assisted simulated digestion method of a milk protein active peptide and an application thereof in health foods, pertaining to the technical field of intensive processing of dairy products and preparation of health foods. The method firstly employs ultrasonic pretreatment of casein and β-lactoglobulin, followed by enzymatic hydrolysis with a protease to prepare casein and β-lactoglobulin polypeptide, and traces the activity of the polypeptide by simulating gastrointestinal digestion, and then simulates absorption by intestinal epithelial cells with Caco-2 cells, to characterize a highly active milk protein polypeptide digested by the gastrointestinal tract and absorbed by the Caco-2 cells simulating absorption by the inner wall of the small intestine. The method has identified five such highly active milk protein polypeptides.

Disclosed are an intermediate drug having synergistic anticancer activity and a polyethylene glycol-coupled synergistic anticancer drug, and a method preparing therefor and use thereof. The intermediate drug has the general structural formula of (I), and the polyethylene glycol-coupled synergistic anticancer drug has the general structural formula of (II). The drugs achieve the combined medication of various anticancer drugs and avoid the toxic reaction caused by the interaction among the drugs or by the pharmacokinetics of the drugs when taking various anticancer drugs, facilitate overcoming the multidrug resistance of cancers, have a synergistic effect, and can be used for preparing anticancer medicaments and for treating cancers.

The purpose of the present invention is to provide an adhesion prevention material capable of exhibiting excellent adhesion preventive effect. This adhesion prevention material concurrently uses: (A) a peptide (A-1) having an amino acid sequence-(X-Pro-Y)n-[wherein X represents an arbitrary defined amino acid, Pro represents proline, Y represents hydroxyproline or proline, and n is an integer between 1 and 10] and/or a peptide (A-2) having an amino acid sequence-(Pro-Y)m-[wherein Pro represents proline, Y represents hydroxyproline or proline, and m is an integer between 1-10]; and (B) a gelatin gel. This adhesion prevention material exhibits a dramatically enhanced adhesion preventive effect as compared with the case where the abovementioned components are used individually, and in particular, has a markedly superior effect against adhesion of tendons.

The invention provides a new oligopeptide linker intermediate and a preparation method thereof. The preparation method of the oligopeptide intermediate is easily carried out under mild reaction conditions, and since almost no side reactions occur in the reaction, the method produces a high-purity product with fewer impurities and easy to be purified, achieving unexpected technical effects.

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, inhibitors of apoptosis proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Disclosed are immune cell-selective small molecule IMPDH inhibitor compounds and methods of their synthesis and use to treat proliferative disorders.