Abstract: A separating agent that serves as an optical resolution agent is composed of a novel, useful optically active polymer. The separating agent is obtained through anionic polymerization of a novel maleimide and serves to separate optically active compounds.

Abstract: Methods of and compositions for pulmonary delivery of therapeutic agents which are capable of forming covalent bonds with a site of interest or which have formed a covalent bond with a pulmonary solution protein are disclosed. Therapeutic agents useful in the invention include wound healing agents, antibiotics, anti-inflammatories, anti-oxidants, anti-proliferatives, immunosupressants, anti-infective and anti-cancer agents.

Abstract: This invention features a compound having the formula: 1

Abstract: A method for producing maleimides. The method comprises reacting maleic anhydride and a primary amine at 100-180° C. in an organic solvent using a solid acidic catalyst, and purifying the maleimide produced therefrom by extraction and crystallization. The molar ratio of the primary amine to maleic anhydride is about 0.8-1.6. With the present invention, high production yield with high purity of maleimides can be achieved. In addition, the solid acidic catalyst can be easily separated and recycled for subsequent use. Thus, the present invention provides a number of distinct advantages, including substantially improved yield, conveniently reusable catalyst, reduced waste disposal and lower costs.

Abstract: A method for producing maleimides. The method comprises reacting maleic anhydride and a primary amine at 100-180° C. in an organic solvent using a solid acidic catalyst, and purifying the maleimide produced therefrom by extraction and crystallization. The molar ratio of the primary amine to maleic anhydride is about 0.8-1.6. With the present invention, high production yield with high purity of maleimides can be achieved. In addition, the solid acidic catalyst can be easily separated and recycled for subsequent use. Thus, the present invention provides a number of distinct advantages, including substantially improved yield, conveniently reusable catalyst, reduced waste disposal and lower costs.

Abstract: The invention relates to novel composite materials comprising

Abstract: A synthesis is described for intermediates which are readily amenable to the large scale preparation of hydroxyethylurea-based chiral HIV protease inhibitors. The method includes forming a diastereoselective epoxide from a chiral alpha amino aldehyde.

Abstract: This invention relates to a diamino compound represented by the formula [1]: in which G1 is a trivalent organic group of 2-20 carbon atoms, G2 is independently a single bond, —COO—, —OCO—, —NHCO—, —CONH—, —O—, —O—, or —CO—, G3 is a single bond or an alkylene group of 1-20 carbon atoms, X and Y are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, a nitro group, or an alkyl group, a haloalkyl group, an alkoxy group or a haloalkoxy group, each alkyl or alkoxy group having 1-12 carbon atoms, or a cycloalkyl group of 3-8 carbon atoms or a trans-4-alkylcyclohexyl group of 9-14 carbon atoms, and m is an integer of 0-3; a polyamic acid and polyimide using the said diamino compound, an aligning film using the said polyimide and a liquid crystal display device using the said aligning film.

Abstract: Unsaturated imidosilanes which are essentially free of siloxanes are taught herein for use surface treatments for inorganic solid materials. Novel methods to make such silanes, which do not yield water or siloxanes as a by-product are also taught. Compositions consisting essentially of imidosilane treated inorganic solid materials, resinuous materials and optionally a free radical generator, especially glass fiber reinforced composites, are taught.

Abstract: A chemic compound having the formula: ##STR1## wherein P.sub.1 is a hydroxyl protecting group, R.sub.1 is an alkyl group, an olefinic group, an aromatic group, Ph, PhCH.sub.2, an O-alkyl group, an O-olefinic group, an O-aromatic group, O--Ph, or O--CH.sub.2 Ph, and wherein Z is an N-imido group. In particular, P.sub.1 may be selected from the group consisting of benzyl, benzyloxymethyl and benzoyl, and Z may be a heterocyclic N-imido group, preferably having 5 to 7 atoms in the ring and alternatively substituted with at least one electron withdrawing group, preferably selected from the group consisting of a chloro group, a fluoro group and a nitro group. In particular, it is contemplated that Z may be succinimido, phthalimido, 5-norbornene-2,3-dicarboxyimido, maleimido and substituted derivatives thereof.

Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.

Abstract: The present application describes amidinophenyl-pyrrolidines, -pyrrolines, and -isoxazolidines and derivatives thereof of formula I: ##STR1## or pharmaceutically acceptable salt forms thereof, wherein one of D and D' may be C(.dbd.NH)NH.sub.2 and the other H, and J.sup.1 and J.sup.2 may be O or CH.sub.2, which are useful as inhibitors of factor Xa.

Abstract: This invention relates to a process for preparing perylene pigment compositions by reaction of(a) a perylene tetracarboxylic compound;(b) about 0.01 to about 20% by weight, relative to the perylene tetracarboxylic compound, of a non-pigmentary cyclic anhydride or imide of formula (I) ##STR1## wherein W is O or NR.sup.1 (where R.sup.1 is hydrogen, a metal, or optionally substituted alkyl, cycloalkyl, aralkyl, or aryl), R.sup.2, R.sup.3, and R.sup.4 are various combinations of substituents and/or fused-on rings, and the dotted line is an optional double bond representing R.sup.2 --C.dbd.C--R.sup.3 ;(c) ammonia or a primary alkyl, aralkyl, or aryl amine; optionally in the presence of(d) a solvent and/or(e) one or more dispersants.

Abstract: An ether is oxidized with oxygen under an oxidation catalyst comprising an imide compound (such as N-hydroxyphthalimide) or the imide compound and a co-catalyst to produce the corresponding chain or cyclic ester or anhydride. The co-catalyst may be a transition metal compound. The above process provides a process for oxidizing an ether by oxygen efficiently to produce the corresponding oxide (such as an ester, an hydride) with high conversion and selectivity.

Abstract: The present invention provides a method for synthesizing indolylmaleimides by reacting an activated maleimide preferably with an optionally substituted organometalic-3-indole in the presence of a transition metal catalyst.

Abstract: Activating groups for cyanine dyes used to label chain terminators in nucleotide sequencing, based on N-hydroxyphthalimide, are disclosed. From these activating groups, activated dyes of the present Invention are prepared which react with the derivitized nucleotide chain terminators to give a labeled chain terminator of the present Invention. The activating groups of the present Invention allow the dye-chain terminator reaction to occur at a much higher yield and with much greater selectivity for the mono-substituted product, compared with the prior art.

Abstract: In accordance with the present invention, there are provided improved methods for the preparation of maleimide monomers. This new method for the synthesis of maleimides is clearly superior to those documented in the prior art. Furthermore, the invention method utilizes materials with reduced toxicity, thus the overall process has a minimal impact on the environment. Thus, in accordance with the present invention, it has been discovered that certain amine salts can be successfully used to replace the polar, aprotic solvents cited in the prior art for the cyclodehydration of maleamic acids. The use of these salts provides competitive reaction times and product yields relative to results obtained with the polar, aprotic solvents. These salts have the advantage of having no vapor pressure and, therefore, have no possibility to co-distill with the water produced by the cyclodehydration reaction. Furthermore, such salts can be tailored to have desirable solubility characteristics (i.e.

Abstract: Provided are methods for the synthesis of N-cyclic maleamic acids and N-cyclic maleimide derivatives, as well as N-cyclic maleamic acids and N-cyclic maleimides synthesized thereby. The method for synthesis of an N-cyclic maleamic acid involves reacting an amino group-containing N-cyclic compound with maleic anhydride in acetic acid to obtain an N-cyclic maleamic acid. An N-cyclic maleimide can be formed by adding hexamethyldisilazane to an N-cyclic maleamic acid prepared according to the above-described method, thereby cyclizing a maleamic acid site of the N-cyclic maleamic acid. The described methods allow for the products to be obtained at high yields.

Abstract: Compounds containing two cyclic hydrocarbon moieties which are substituted to provide crosslinking functionality and which are linked to each other by secondary or tertiary oxycarbonyl containing moiety are basis for compositions which are cured to provide cured thermosets for encapsulation and underfill for electronic components that are thermally decomposable to allow repair, replacement, recovery or recycling of operative electronic components from assemblies that are inoperative.

Abstract: The invention relates to novel dimaleinimido-substituted dihydroxyalkanes, to a process for their preparation as well as to their use as cross-linking reagents, e.g. in analytical methods. A disadvantage of the cleavable bismaleinimido derivatives used so far, which react with SH groups, is that the subsequent cleavage of the cross-linking reagents from the proteins must take place in acidic or alkaline media. The objective of the invention is to prepare novel cleavable cross-linking reagents which react with SH groups or proteins and which form cross-links which can be cleaved under mild conditions not requiring strongly acidic or basic media. This objective is sought through the preparation and use of dimaleinimido-substituted dihydroxyalkanes having the general formula I ##STR1## where n=1 to 6, preferably 1 or 2.

Abstract: The salt of a sulfonated succinic acid is cyclized, then converted to novel sulfonated hydroxamic acids by reaction with hydroxylamine (which is added or formed in situ), and the novel hydroxamic acid is then cyclized to the sulfo-N-hydroxysuccinimide salt. This synthetic procedure is simple, direct, and more rapid than present procedures for synthesis of the succinimide. Novel sulfo-hydroxamic acid intermediates are formed during this procedure.

Abstract: There is provided a process for producing a tertiary amine compound in one step without using any subsidiary raw material or any solvent, by subjecting a secondary amine compound and an alcohol to an intermolecular dehydration reaction in a gas phase. The process uses, as a catalyst, an oxide containing an alkali metal element and/or an alkaline earth metal element and silicon.

Abstract: Branched hydrazone linkers for linking a targeting ligand such as an antibody to a therapeutically active drug. The point of branching is at a polyvalent atom and the number of drugs increases by a factor of two for each generation of branching. A preferred drug is doxorubicin.

Abstract: A process for producing a compound of the formu5la ##STR1## comprising the step of reacting a compound of the formula ##STR2## with a compound of the formula ##STR3## to form a compound of the formula ##STR4## wherein R.sup.2a is selected from the groups recited above for R.sup.2, or R.sup.2a --X-- is a protected hydroxyl group, and Z is a group of formula --Y--R.sub.5 recited above, or a group that can be converted into a group of said formula --Y--R.sup.5. Intermediates of formula IV and composition containing substantially optically pure enantiomers of Formula (I) are included within the scope of the invention.

Abstract: N-Substituted cyclic imides are obtained by reacting a cyclic acid anhydride with an amine in the presence of a solvent and an acid catalyst at 80.degree. to 200.degree. C. and with removal of the water formed, it being particularly advantageous to carry out this reaction in the presence of a stabilizer and an inert, dipolar aprotic cosolvent, optionally to add an inert organic solvent of low or zero polarity to the reaction mixture present after the reaction, to add a non-aqueous base in an amount of 0.5 to 50% by weight, based on the cyclic anhydride of the formula (II) used, and to separate off the precipitate formed to give a filtrate containing the N-substituted cyclic imide.

Abstract: A process for preparing N-substituted maleimide is disclosed, which includes reacting maleic anhydride with a primary amine using both a non-polar solvent and a protic polar solvent in the presence of an acid catalyst.

Abstract: Disubstituted heterocyclic thrombin inhibitors are provided which have the structure ##STR1## wherein G is ##STR2## wherein n is 0, 1 or 2 or 3; m is 0, 1, 2 or 3; Y is NH or S; p is 0, 1 or 2, Q is a single bond or ##STR3## and Z, A, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6 are as defined herein.

Abstract: A process for the preparation of a N-)ortho-alkylphenyl)-imide of the formula ##STR1## in which R.sup.1 to R.sup.9 is defined in the specification which comprises reacting a cyclic anhydride of the formula ##STR2## wherein R.sup.6 to R.sup.9 are difined in the specification with an amine of the formula ##STR3## optionally in the presence of an acid catalyst and optionally in the presence of a solvent which is immiscible or only slightly miscible with water but can form an azeotrope with water, at a temperature between 100.degree. to 200.degree. C. under conditions so that the water formed during the reaction is removed from the reaction mixture without the addition of a polymerization inhibitor or a dipolar solvent. The final products are used as intermediates to prepare heat-stable plastics as well as intermediates to prepare pharmaceutical and agricultural chemicals.

Abstract: The invention is concerned with novel heterotrifunctional compounds which contain a chemically reactive group R, a photochemically reactive group Ar--N.sup.3 and a reductively cleavable S--S(X.sub.2)-group. The chemically reactive group and the photochemically reactive group are separated by a spacer group which contains a disulfide group. The water-solubilizing groups are carboxylic acids and sulfonic acids or derivatives thereof which are attached either to the aromatic ring or to the spacer group between the aromatic ring and the cleavable SS group. The compounds facilitate a novel photoaffinity method for the labelling of biomolecules, whereby the labelled biomolecule preserves its water solubility and the labelling molecule preferably projects free into the solution after anchorage to the surface of the biomolecule.

Abstract: Cycloalkyltriols containing heterocyclic substituents, in particular cyclopentyl- and cyclohexyltriols containing heterocyclic substituentsCompounds of the formulae I and II ##STR1## in which the substituents A, R.sup.1, R.sup.2 and R.sup.3 and n have the meanings given, have an antiviral and antiparasitic action.

Abstract: Haloaryl compounds are lithiated and thereafter metalated with one of the following organometallic groups: Sn(n--Bu).sub.3 or SnMe.sub.3. The resulting aryltin compound can be transmetalated in site-specific reaction with one of the following organometallic groups: HgX, Hg(OAc).sub.2, BX.sub.3, or BZ.sub.2, wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The metalated compounds are subsequently radiohalogenated via a demetalation reaction. A functional group suitable for conjugation to protein can be added subsequent or preferably prior to the radiohalogenation.Also compounds of the formula: R.sub.1 --Ar--R.sub.2, wherein R.sub.1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R.sub.2 is a short-chain substituent that does not activate the aromatic ring and that bears a functional group, or a precursor thereof, suitable for conjugation to protein under conditions that preserve the biological activity of the protein.

Abstract: Dyes suitable for use in the fabrication of color filters are described which contain one or more photopolymerizable substituents preferably represented by the following formula:D-(A-Yn.sup.1)n.sup.2 (1)where D represents a chromphoric nucleus, A denotes a connecting group, Y means the photopolymerizable group, n.sup.1 is 1-10,000, and n.sup.2 stands for an integer of 1-10. Also described are photosensitive resist resin compositions containing the dyes as well as color filters fabricated by curing the photosensitive resist resin compositions.

Abstract: The present invention provides a stabilized maleimide compound which is hard to discolor during storage. The maleimide compound has a content of primary amines of not more than 500 ppm or further has a content of maleic anhydride in the range of 5 to 2,000 ppm or a content of 2-amino-N-substituted succinimide compounds of not more than 300 ppm. Furthermore, it is preferable that the content of chlorine compounds reduced as a chlorine atom is not more than 10 ppm and further the content of volatile components having a boiling point of not more than 200.degree. C. at normal pressure is not more than 2,000 ppm.

Abstract: A method is provided for preparing homochiral maleimide intermediates of the structure ##STR1## wherein R.sup.7, R.sup.8 and R.sup.9 are as defined herein by reacting a homochiral amine of the structure ##STR2## with maleic anhydride and a silylating agent. The maleimide intermediate is used in the enantio-selective preparation of thromboxane A.sub.2 receptor antagonists.

Abstract: In the production of an N-unsubstituted maleinimide by the ring-closing alcohol-removing treatment of an N-unsubstituted maleinamic ester for conversion into an imide, an acid catalyst or a mono(cyclo)alkyl sulfuric ester is used for the reaction. In this case, the alcohol concentration in the reaction solution is preferable to be adjusted to a low level. By using a maleinamic acid and an alcohol in conjunction with an inert solvent and an acid catalyst, a mixture of maleinamic acid with an acid catalyst, or a mono(cyclo)alkyl sulfuric ester, a corresponding maleinamic ester is obtained.

Abstract: Carbonarins A, B, C, D, E, F, G, and H have been isolated from the sclerotia of the fungus Aspergillus carbonarius. The carbonarins are effective for controlling Coleopteran and Lepidopteran insects. The carbonarins have the structure: ##STR1## wherein: R.sub.1 is a hydrogen atom or a hydroxy group; R.sub.2 is a hydrogen atom or a methoxy group; R.sub.3 is a hydrogen atom or a naphthopyrone group; and X is an oxygen atom or an NH group.

Abstract: Disclosed is an aromatic diamine compound represented by the formula (I) ##STR1## wherein R is H or CH.sub.3. Also disclosed is a bismaleimide compound represented by the formula (IV) ##STR2## wherein R is H or CH.sub.3, A resin forming composition comprising these compounds is also disclosed. The compounds are useful as raw materials for resins, and the resin forming composition and the resin can provide excellent heat resistance and impact resistance and low hygroscopicity.

Abstract: The present invention includes N-substituted maleimides (1(H)-Pyrrole-2,5-dione (Maleimide) analogs and succinimides which act as potent nonsteroidal anti-inflammatory drugs and are capable of dual inactivation or selective inactivation of the cyclooxygenase and the peroxidase activities of prostaglandin endoperoxide synthase (PGHS).

Abstract: The invention relates to fluorescent and/or reactive derivatives of 1,2-bis-(2-aminophenoxyethane)-N,N,N',N'-tetraacetic acid (BAPTA) according to the formula: ##STR1## where at least one of W and X is a functional group, with or without a spacer, that terminates in an alcohol or phenol, a thiol, a haloacetamide, an alkyl halide, an amine or aniline, a carboxylic acid, an anhydride, an isocyanate, an isothiocyanate, a maleimide, or an activated ester. The BAPTA-like molecule may be further substituted, one or more times, by additional functional groups with or without spacers or by CH.sub.3, NO.sub.2, CF.sub.3, F, Cl, Br, I, or carboxylic acid derivatives or pharmaceutically acceptable salts thereof, or by indolyl or benzofuran fluorophores. The functional groups allow for subsequent covalent attachment of one or more oxygen heterocycle fluorophores (e.g. fluorescein, coumarin, rhodamine); or polymolecular assemblies (e.g.

Abstract: Bifunctional aromatic compounds which are capable of linking metal ions to biologically useful molecules. The bifunctional compounds are characterized as having a hydrazine or hydrazide group and a protein reactive group. The hydrazine or hydrazide group may be protected as a lower alkyl hydrazone. Conjugates of the bifunctional compounds with macromolecules are also described and labelled macromolecules comprised of the conjugates and metal ions are provided. Additionally, a method is provided for forming a labelled macromolecule by reacting a conjugate with a metal species. The compounds and method of this invention are particularly useful in the fields of biology and medicine for imaging and/or therapy.

Abstract: A polymerzable compound represented by the general formula (1) X--R.sub.1 --Y where X is un unsaturated imide group having substituents R.sub.2 and R.sub.3, or an itacon imide group where R.sub.2 and R.sub.3 are selected from the group consisting of hydrogen, a lower alkyl group and an aromatic group having a substituent p which is hydrogen, a lower alkyl group, or an alkoxy group, and Y is a styryl group, and R.sub.1 is a divalent organic group.The polymerizable compounds is excellent in formability, and find a wide variety of applications because they have functional groups different in reactivity from each other and hence allow the curing conditions to control. The cured polymers are excellent in thermal durability, mechanical properties and electrical properties, making it possible to achieve higher performance, higher reliability, highly compact and lower weight of electric apparatuses and electronic parts.

Abstract: Compounds containing at least one alkenyl group, at least one maleimide group and at least one rodlike mesogenic moiety are prepared by reacting one or more aminophenols containing one or more rodlike mesogenic moieties with a stoichiometric quantity of a maleic anhydride per amine group of said aminophenol and then alkenylating the resulting phenolic functional maleimide.

Abstract: Provided are novel superoxide dismutase derivatives represented by the following general formula (I) ##STR1## wherein [SOD] is a superoxide dismutase residue derived by removal of two mercapto groups, and W is a divalent long chain hydrocarbon residue which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen atom, a sulfur atom and a group of -N(R)- (R being a lower alkyl group). The SOD derivatives retain most of the enzymatic activities of unmodified SOD and have much longer plasma half-life than unmodified SOD. They are effective for treating various diseases caused by active oxygen species.Also provided are chemical modifiers to prepare the above SOD derivatives.

Abstract: The present invention provides bioactive compounds of the general formula: ##STR1## wherein R is H, (C.sub.1 -C.sub.4)alkyl, (C.sub.3 -C.sub.6)cycloalkyl, (C.sub.3 -C.sub.6)cycloalkyl(C.sub.1 -C.sub.4)alkyl, allyl, (C.sub.6 -C.sub.10)aryl or (C.sub.1 -C.sub.4)alkylCO.sub.2 Y; Y is H, (C.sub.1 -C.sub.4)alkyl or (C.sub.6 -C.sub.10)aryl; each X is individually H, (C.sub.1 -C.sub.4)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.3 -C.sub.6)cycloalkyl(C.sub.1 -C.sub.4)alkyl, or (C.sub.3 -C.sub.6)cycloatkyl; the bond represented by--is present or is absent; and the pharmaceutically acceptable salts thereof, and methods for using said compounds to stimulate receptors in the mammalian nervous systems.

Abstract: There is provided a safe and effective means of introducing an alkoxymethyl group onto the ring Nitrogen atom of a wide variety of pyrrole compounds via the reaction of the appropriate pyrrole precursor sequentially with dialkoxymethane, Vilsmeier reagent and a tertiary amine. The product 1-(alkoxymethyl)pyrroles are useful as insecticidal, acaricidal, nematocidal and molluscicidal agents.

Abstract: The invention is from the field of heterobifunctional cross-linking reagents. More particularly, the invention concerns cross-linking reagents which combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, thereby allowing coupling of aldehydes to free thiols.

Abstract: Reactive multifunctional imide monomers have been discovered from which radiation curable oligomers and polymers may be derived. The reactive imide monomers have at least one functional group which is polymerizable under free radical or ionic polymerization conditions with other similar functional groups. However, the same functional group and reaction product derived therefrom is substantially not subject to cleavage by oxidation or hydrolysis. The reactive imide monomer also contains at least one other functional group which remains intact under the above-described polymerization conditions to form a part of a side chain of the resultant polymer and will cross-link or cure by 2+2 cyclo-addition with other like functional groups upon irradiation.

Abstract: The present invention provides (1) curable polyamide monomers represented by the formula: R.sup.1 --A.sup.1 --B.sup.1 --A.sup.2 --B.sup.2 --A.sup.3 --R.sup.2 where R.sup.1 and R.sup.2 are radicals selected from the group consisting of maleimide, substituted maleimide, nadimide, substituted nadimide, ethynyl, and (C(R.sup.3).sub.2).sub.2 where R.sub.3 is hydrogen with the proviso that the two carbon atoms of (C(R.sup.3).sub.2).sub.2 are bound on the aromatic ring of A.sup.1 or A.sup.3 to adjacent carbon atoms, A.sup.1 and A.sup.3 are 1,4-phenylene and the same where said group contains one or more substituents selected from the group consisting of halo, e.g., fluoro, chloro, bromo, or iodo, nitro, lower alkyl, e.g., methyl, ethyl, and propyl, lower alkoxy, e.g., methoxy, ethoxy, or propoxy, and fluoroalkyl or fluoroalkoxy, e.g., trifluoromethyl, pentafluoroethyl and the like, A.sup.

Abstract: 2,5-Dioxo-3-pyrroline-1-acetanilide compounds which are effective for the control or prevention of phytopathogenic fungi are described. A method for the fungicidal use of said compounds, fungicidal compositions containing said compounds and a method for the preparation of said compounds are also presented.

Abstract: Provided is a long chain carboxylic acid imide ester (I) represented by the following general formula (I) ##STR1## wherein W is a divalent long chain hydrocarbon group which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen, atom, a sulfur atom, and a group of --N(R.sup.1)-- (R.sup.1 being a lower alkyl group) and X represents a divalent hydrocarbon group which may optionally be substituted, or salt thereof. The above long chain carboxylic acid imide ester or its salts is useful for modifying enzymes or proteins having biological activities to give their derivatives which have, while retaining most of the original biological activities, an extremely prolonged plasma half-life as compared with the proteins and have no antigenecities and can be administered to animals.