A branched monodispersed polyethylene glycol represented by the formula (1): ##STR00001##
wherein X.sup.1 is a functional group that forms a covalent bond upon a reaction with a functional group present in a biofunctional molecule; n is an integer of 4 to 50, which represents number of repeating units of ethylene oxide units; and L.sup.1 represents a single bond, NH, -L.sup.2-(CH.sub.2).sub.m1- or -L.sup.2-(CH.sub.2).sub.m1-L.sup.3-(CH.sub.2).sub.m2-, L.sup.2 represents an ether bond, an amide bond, an urethane bond or a single bond, L.sup.3 represents an ether bond, an amide bond or an urethane bond, and m1 and m2 represent each independently an integer of 1 to 5.

A PEG linker as represented by formula (I), wherein n and m are respectively an integer from 1 to 7, providing the PEG linker with 1 to 49 linking sites. A ligand drug conjugate as represented by formula (II). The conjugate uses the PEG linker to increase a drug loading capacity and drug loading diversity, thereby improving pharmaceutical efficacy.

Y1-PEG1-{R.sup.1-PEG2-{Y4}.sub.n}.sub.m(I)

TM-{R.sup.2-PEG1-{R.sup.1-PEG2-{R.sup.3-A-drug}.sub.n}.sub.m}.sub.l(II)

The instant disclosure provides (among other things) novel water-soluble polymer reagents capable of selective conjugation to histidine residues. e.g., in peptides and proteins, as well the resulting conjugates and related compositions. In addition, provided are methods of preparing the polymer reagents, as well as methods for conjugating the polymer reagents to active agents and other substances, pharmaceutical compositions, and methods for administering the conjugates.

Methods are provided for the preparation of conjugates of a variety of bioactive components, especially proteins, with water-soluble polymers (e.g., poly(ethylene glycol) and derivatives thereof), which conjugates have reduced antigenicity and immunogenicity compared to similar conjugates prepared using poly(ethylene glycol) containing a methoxyl or another alkoxyl group. The invention also provides conjugates prepared by such methods, compositions comprising such conjugates, kits containing such conjugates or compositions and methods of use of the conjugates and compositions in diagnostic and therapeutic protocols.

The present invention generally relates to macromolecules of dendrimer-drug conjugates. In particular, the invention relates to macromolecules comprising a pharmaceutically active agent, such as a protein or peptide, attached to a core of a dendrimer derived from branched building units, such as lysine or lysine analogues. The invention also relates to the synthesis of the dendrimers and macromolecules, and the use of such macromolecules, particularly in therapeutic applications, and pharmaceutical compositions comprising them.

The present invention provides adhesive hydrogels that negatively swell at physiological temperature. By combining mussel-mimetic chemistry and the thermosensitive nature of poly(ethylene oxide)-poly(propylene oxide) copolymers, novel materials were designed that are suitable as medical sealants and adhesives.

The invention describes benzene-1,3,5-tricarboxamide (BTA) based hydrogels. The hydrogels have purpose in tissue culturing for in vitro applications such as drug screening or in vivo applications such as transplantation. The hydrogels are particularly tough but still allow 3D printing and cell culturing. The invention further describes 3D printing of the hydrogels and uses of the hydrogels.

The present disclosure relates to degradable polymers which contain a hydrophobic and hydrophilic segment which is sensitive to pH. In some aspects, the polymers form a micelle which is sensitive to pH and have backbones which are capable of undergoing degradation in vivo. In some aspects, the disclosure also provides methods of using these degradable polymers for the delivery of a drug.

An intracellularly degraded branched and degradable polyethylene glycol derivative represented by the following formula (1): ##STR00001##
wherein each symbol is as defined in the present specification, that is used for modifying bio-related substances is provided by the present invention.