Beta-lactamase targeted photosensitizer for pesticide and pest detection

Abstract

Photoactivatable pesticide compounds and methods for the use thereof in the elimination and detection of pests are provided.

1 . A pesticidal composition comprising a pesticidally effective amount of one or more photosensitizers that are linked by one or more moieties cleavable by a β-lactamase expressed by a pest wherein said linked moieties are present in an amount sufficient to quench photoactivation of said photosensitizers and wherein said one or more photosenitizers are capable of generating a phototoxic species upon dequenching and light-activation. 
     
     
         2 . The pesticidal composition of  claim 1 , wherein the one or more moieties cleavable by the β-lactamase comprise: a cephalosporin, a penicillin, a penem, a carbapenem, a monocyclic mobactem, or a fragment thereof. 
     
     
         3 . The photosensitizer composition of  claim 2 , wherein the one or more moieties cleavable by the β-lactamase comprises a cephalosporin, a penicillin, or a fragment thereof. 
     
     
         4 . The pesticidal composition of  claim 3 , wherein the cephalosporin or penicillin fragment comprises a beta-lactam ring. 
     
     
         5 . The pesticidal composition of  claim 3 , wherein the one or more moieties cleavable by β-lactamase is a cephalosporin. 
     
     
         6 . The pesticidal composition of  claim 5 , wherein at least one photosensitizer is bound at the 3′ position of a cephalosporin. 
     
     
         7 . The pesticidal composition of  claim 1 , wherein the photosensitizer is a porphyrin. 
     
     
         8 . The pesticidal composition of  claim 7 , wherein the porphyrin is selected from the group consisting of a porfimer sodium, hematoporphyrin IX, hematoporphyrin ester, dihematoporphyrin ester, synthetic diporphyrin, O-substituted tetraphenyl porphyrin, 3,1-meso tetrakis porphyrin, hydroporphyrin, benzoporphyrin derivative, benzoporphyrin monoacid derivative, monoacid ring derivative, tetracyanoethylene adduct of benzoporphyrin, dimethyl acetylenedicarboxylate adduct of benzoporphyrin, δ-aminolevulinic acid, benzonaphthoporphyrazine, naturally occurring porphyrin, ALA-induced protoporphyrin IX, synthetic dichlorin, bacteriochlorin tetra(hydroxyphenyl) porphyrin, purpurin, octaethylpurpurin derivative, etiopurpurin, tin-etio-purpurin, porphycene, chlorin, chlorin e 6 , mono-1-aspartyl derivative of chlorin e 6 , di-1-aspartyl derivative of chlorin e 6 , tin(IV) chlorin e 6 , meta-tetrahydroxyphenylchlorin, chlorin e 6  monoethylendiamine monamide, verdin, zinc methyl pyroverdin, copro II verdin trimethyl ester, deuteroverdin methyl ester, pheophorbide derivative, pyropheophorbide, texaphyrin, lutetium (III) texaphyrin, and gadolinium(III) texaphyrin. 
     
     
         9 . The pesticidal composition of  claim 1 , wherein the photosensitizer is a photoactive dye. 
     
     
         10 . The pesticidal composition of  claim 9 , wherein the photoactive dye is selected from the group consisting of a merocyanine, phthalocyanine, chloroaluminum phthalocyanine, sulfonated aluminum PC, ring-substituted cationic PC, sulfonated AlPc, disulfonated or tetrasulfonated derivative, sulfonated aluminum naphthalocyanine, naphthalocyanine, tetracyanoethylene adduct, crystal violet, azure β chloride, benzophenothiazinium, benzophenothiazinium chloride (EtNBS), phenothiazine derivative, rose Bengal, toluidine blue derviatives, toluidine blue O (TBO), methylene blue (MB), new methylene blue N (NMMB), new methylene blue BB, new methylene blue FR, 1,9-dimethylmethylene blue chloride (DMMB), methylene blue derivatives, methylene green, methylene violet Bernthsen, methylene violet 3RAX, Nile blue, Nile blue derivatives, malachite green, Azure blue A, Azure blue B, Azure blue C, safranine O, neutral red, 5-ethylamino-9-diethylaminobenzo[a]phenothiazinium chloride, 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium chloride, thiopyronine, and thionine. 
     
     
         11 . The pesticidal composition of  claim 1 , wherein the photosensitizer is selected from the group consisting of a Diels-Alder adduct, dimethyl acetylene dicarboxylate adduct, anthracenedione, anthrapyrazole, aminoanthraquinone, phenoxazine dye, chalcogenapyrylium dye, cationic selena, tellurapyrylium derivative, cationic imminium salt and tetracycline. 
     
     
         12 . The composition of  claim 1 , wherein the composition comprises a one or more of the same photosensitizer. 
     
     
         13 . The composition of  claim 1 , wherein the β-lactamase comprises SEQ ID NO:1 or a fragment thereof. 
     
     
         14 . The composition of  claim 1 , wherein the β-lactamase comprises a protein domain having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, identity to SEQ ID NO:1. 
     
     
         15 . The composition of  claim 1 , wherein the β-lactamase comprises SEQ ID NO: 2 or a fragment thereof. 
     
     
         16 . The composition of  claim 1 , wherein the β-lactamase comprises a protein domain having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, identity to SEQ ID NO:2. 
     
     
         17 . A pesticidal composition comprising a pesticidally effective amount of a backbone coupled to one or more photosensitizers and one or more binders effective to quench photoactivation, wherein the binders are connected to the backbone through a one or more moieties cleavable by a β-lactamase expressed by a pest and wherein said one or more photosenitizers are capable of generating a phototoxic species upon dequenching and light-activation. 
     
     
         18 . The pesticidal composition of  claim 1 , further comprising a pesticidally acceptable carrier or excipient. 
     
     
         19 . A method for eliminating a pest from a host, said method comprising the steps of:
 contacting the pest with an effective amount of a pesticidal composition of  claim 1 ;   cleaving one or more moieties cleavable by β-lactamase to dequench the photosensitizer composition; and   light-activating the composition to produce a phototoxic species, thereby eliminating the pest from said host.   
     
     
         20 . The method of  claim 19 , wherein the phototoxic species is also fluorescent. 
     
     
         21 . The method of  claim 19 , wherein the pest is an arthropod, a nematode, or an insect and the host is a plant. 
     
     
         22 . The method of  claim 21 , wherein the arthropod or insect is selected from the group consisting of nematodes, grubs, weevils, borers, aphids, moths, mosquitoes, flies, ticks, termites, beetles, caterpillar, cutworms, earworms, armyworms, and budworms. 
     
     
         23 . The method of  claim 21 , wherein the plant is selected from the group consisting of corn, maize, wheat, tobacco, cotton, rice, soybean, peanut, sugarcane, hay, sorghum, lettuces, kales, cabbages, fruit trees, and horitcultural flowers. 
     
     
         24 . The method of  claim 19 , wherein the pest is a parasite and the host is an animal. 
     
     
         25 . The method of  claim 24 , wherein the parasite is selected from the group consisting of ticks, lice, mites, ascarids, filarias, hookworms, pinworms, whipworms, strongyles,  Trichinella spiralis, Dirofilaria immitis, Haemonchus contortus, Brugia malayi  and  Myrmeconema neotropicum.    
     
     
         26 . The method of  claim 24 , wherein the host is a human. 
     
     
         27 . A method for eliminating a pest from an industrial material, said method comprising the steps of:
 contacting the pest with a pesticidal composition of  claim 1 ;   cleaving one or more moieties cleavable by β-lactamase to dequench the photosensitizer composition; and   light-activating the composition to produce a phototoxic species, thereby eliminating the pest from said host.   
     
     
         28 . The method of  claim 27 , wherein the pest is selected from the group consisting of beetles, termites, and hymenopterons. 
     
     
         29 . The method of  claim 27 , wherein the industrial material is selected from the group consisting of plastics, adhesives, sizes, paper and card, leather, wood and processed wood products. 
     
     
         30 . A method for eliminating a pest from an enclosed space, said method comprising the steps of:
 contacting the pest with a pesticidal composition of  claim 1 ;   cleaving one or more moieties cleavable by β-lactamase to dequench the photosensitizer composition; and   light-activating the composition to produce a phototoxic species, thereby eliminating the pest from said space.   
     
     
         31 . The method of  claim 30 , wherein the pest is selected from the group consisting of scorpions, spiders, woodlice, pillbugs, bedbugs, millipedes, centipedes, caterpillars, moths, silverfish, cockroaches, grasshoppers, locusts, flies and mosquitoes. 
     
     
         32 . A method for detecting a pest, said method comprising the steps of:
 contacting the pest with a quenched photosensitizer composition comprising a plurality of photosensitizers that are linked by one or more moieties cleavable by a β-lactamase expressed by the pest, wherein said linked photosensitizers are present in an amount sufficient to quench photoactivation of said photosensitizers;   cleaving one or more moieties cleavable by the β-lactamase to dequench the photosensitizer composition; and light-activating the composition to produce a fluorescent species, and   detecting the pest by observing the fluorescence, thereby detecting the presence of the pest.   
     
     
         33 . The method of  claim 32 , wherein the florescent species is also phototoxic. 
     
     
         34 . A method for controlling an insect pest, the method comprising
 contacting the pest with an effective amount of a pesticidal composition of  claim 1 ;   cleaving one or more moieties cleavable by β-lactamase to dequench the photosensitizer composition; and   light-activating the composition to produce a phototoxic species, thereby controlling the insect pest.   
     
     
         35 . The method of  claim 34 , wherein the insect is  Aedes albopictus.    
     
     
         36 . A method for controlling a filarial nematode, the method comprising contacting the with worm with an effective amount of a pesticidal composition of  claim 1 ;
 cleaving one or more moieties cleavable by β-lactamase to dequench the photosensitizer composition; and   light-activating the composition to produce a phototoxic species, thereby controlling the worm.   
     
     
         37 . The method of  claim 36 , wherein the filarial nematode is  Wuchereria bancrofti, Brugia malayi , or  B. timori.    
     
     
         38 . A method for ameliorating filariais in a subject, the method comprising administering to the subject an effective amount of a composition of  claim 1 ;
 cleaving one or more moieties cleavable by β-lactamase to dequench the photosensitizer composition; and   light-activating the composition to produce a phototoxic species, thereby ameliorating the filariasis.   
     
     
         39 . The method of  claim 38 , wherein the method reduces the filarial load in the subject by at least about 10-25% or more. 
     
     
         40 . The method of  claim 38 , wherein the filariasis is associated with  Wuchereria bancrofti, Brugia malayi , and/or  B. timori.    
     
     
         41 . A method for controlling a fouling pest on an object in contact with saltwater or brackish water, the method comprising contacting the pest with an effective amount of a pesticidal composition of  claim 1 ;
 cleaving one or more moieties cleavable by β-lactamase to dequench the photosensitizer composition; and   light-activating the composition to produce a phototoxic species, thereby controlling the pest.   
     
     
         42 . The method of  claim 41 , wherein the fouling pest is a goose barnacle, an acorn barnacle or a sessile Oligochaeta. 
     
     
         43 . The method of  claim 1  wherein the light-activation is from exposure to sunlight. 
     
     
         44 . The method of  claim 1  wherein the light-activation is from administration of LED lighting. 
     
     
         45 . The method of  claim 1  wherein the light-activation is from administration of laser lighting. 
     
     
         46 . The method of  claim 1 , wherein the composition comprises a beta-lactamase enzyme-activated-photosensitizer (β-LEAP). 
     
     
         47 . A kit for eliminating a pest comprising the pesticidal composition of  claim 1  and instructions for using the pesticidal composition to eliminate the pest. 
     
     
         48 . A kit for detecting a pest comprising a photosensitizer composition comprising one or more photosensitizers that are linked by one or more moieties cleavable by a β-lactamase expressed by the pest, wherein said linked moieties are present in an amount sufficient to quench photoactivation of said photosensitizers and wherein said one or more photosenitizers are capable of generating a fluorescent species upon dequenching and light-activation, and instructions for using the photosensitizer composition to detect the pest.